Note: Descriptions are shown in the official language in which they were submitted.
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DescriQtion
Stealth Virus Nucleic Acids and Related Methods
Technical Field
The present invention primarily relates to diagnosis of infections that are
caused by atypically
structured cytopathic viruses. It provides viral isolates and sequence data on
representative isolates.
Methods are described for obtaining nucleic acid sequences contained within
additional isolates of
this molecularly heterogeneous grouping of cytopathic viruses and for using
the sequence data for
the design and implementation of sensitive virus detection methods, and for
determining modes of
vinrs transmission, choices of therapy, and likely mechanisms of induced cell
damage. Sequence data
are also useful in the classification. characterization and quantitation of
individual viral isolates, and
in determining other potential uses of isolated viruses, such as their use as
vectors for the transfer of
genetic information.
Background Art
This section provides an up-to-date overview of conventional viruses, their
modes of
detection, using culture, immunological and molecular probe based assays, and
the utility of deriving
nucleic acid sequence information on viral isolates.
A. Viruses
1. Definition: Viruses are very small organism, which can grow and multiply,
only inside of
a cell. They require the contents of the cell to manufacture the various
components of the virus. These
components are; i) DNA or RNA nucleic acids, comprising a chain or polymer of
nucleotides
connected through a phohodiester bond from the 5' to 3' carbon atoms of the
sugar moiety of the
nucleotide. These are the genes of the virus. Viral particles contain either
RNA or DNA but not both,
whereas bacteria and cells have both RNA and DNA. The amount of DNA or RNA in
a virus varies
depending on the type of virus. Small viruses, e.g. papillomavirus have about
9,000 nucleotide
molecules strung in a row. Big viruses, e.g. a herpesvirus can have 200,000
nucleotides. ii) A protein
(or proteins) which associate with the DNA or RNA and provides some protection
as the virus passes
between cells. The proteins make up the capsid of the virus and are formed by
the aggregation of
normally soluble proteins into a shell-like structure iii) Some viruses also
have an outer protective
layer of proteins in a lipid envelope, and sometimes also between the capsid
and the envelope (termed
tegument proteins). Finally, some but not all viruses possess various enzymes
involved directly or
indirectly in the replication of the viral nucleic acids
2. Classification: Viruses are classified in several ways, for example. i)
Whether the viral
particles contain RNA or DNA. Some RNA viruses convert to DNA after they enter
a cell and are
called retroviruses. ii) Whether the genome is single (ss) or double stranded
(ds). iii) For single
stranded RNA viruses, the sequence may directly code for its protein
(positive, +ve, stranded), or
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consist of the opposite or negative, -ve, strand. iv) The genome may be linear
or circular and may be
in a single segment, or in multiple segments. iv) The genome size and overall
shape of the virus and
whether an envelope is present are also major criteria used for
classification. v) Finally, the kinds of
diseases produced can distinguish different viruses. Related viruses are
successively grouped into
species, genera, families and orders.
3. Viral Diseases: Viruses which cause disease are termed pathogenic. Examples
of virus
induced diseases include; influenza, the common cold, chickenpox, measles,
mumps, rubella, hepatitis,
infectious mononucleosis, polio, etc. Some viruses are thought to play a
contributing role in causing
certain types of cancers, such as papillomavirus in cervical cancer, and
Epstein-Barr virus in Burkitt's
lymphoma. Viruses are not widely regarded as a cause of lung cancers, breast
cancers, gastrointestinal
tumors, brain tumors and melanomas. A retrovirus called human~immunodeficiency
virus (HIV)
damages the immune system and causes the Acquired Immunodeficiency Syndrome
(AIDS).
4. Mechanism of Viral-Induced Diseases. Some viruses can directly damaue cells
by triggering
a cellular destructive process termed apoptosis; andlor by usurping the cells
metabolic resources;
and/or by producing toxic components; all of these processes can interfere
with the cells' normal
functions. Cell damaging viruses will generally induce a morphological
alteration in infected cells
which is commonly referred to as a cytopathic efFect (CPE). This change can be
seen in infected
tissues and under suitable cell culture conditions can be seen in cells grown
in vitro in tissue cultures.
Viruses can also cause cells to express viral and/or altered cellular
components that may become
targets for anti-cellular immunity. HIV directly attacks the immune system
leaving the infected host
vulnerable to secondary infections by other pathogens. Viruses that have been
associated with cancers
are thought to act mainly by causing mutations in critical cellular genes.
5. Distinction between Prions and Viruses. Certain types of cellular proteins
have the
property, similar to viral capsid proteins, that when present in a particular
configuration; will
complex with corresponding soluble protein resulting in the assembly of
insoluble structures formed
by induced aggregation of the molecules. Abnormally configured cellular
protein can initiate a chain
reaction leading to the progressive accumulation of protease-resistant
material termed amyloid. Such
proteins have been termed "prions" for "proteinaceous infectious particles".
Certain humans and
animals inherit genetically altered normal protein with an enhanced tendency
to "spontaneously"
generate the small quantity of the abnormally configured protein to begin the
process. If other
individuals simply become exposed to these proteins, e.g. by ingestion with
food, disease can occur
through the progressive conversion of the new host' s proteins, along with the
potential of further
transmission. Prion diseases include scrapie in sheep, bovine spongiform
encephalopathy or mad cow
disease in cows and both Creutzfeldt-lakob disease and kuru in humans. A role
for nucleic acids in
prion disease transmission has been discounted by the scientific community
largely because the
protein itself appears capable of causing disease and, to date, no
transmissible viral nucleic acids have
been identified in association with these diseases..
B. Laboratory Diagnosis of Viral Infection:
lmmunological, tissue culture and molecular biological methods are used to
diagnose viral
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infections and to ascertain the extent of viral damage and the quality and
intensity of the body's
immune response against the viral proteins.
The antibody response to a viral infection normally starts with the relatively
transient
production of IgM followed by a long lasting production of IgG. For this
reason, a specific IgM
antibody response to viral components (termed antigens) can generally be taken
as a sign of early
infection. The serological detection of free viral antigen can precede the
earliest serological response
and this type of assay can be useful for certain infections, e.g. parvovirus B
19, HIV, hepatitis B virus
(HIiV) and human herpesvirus-6 {HHV-6). Antigen assays can also be used to
distinguish persisting
infection, in spite of IgG response, from a cured infection. Again, this type
of approach has been
employed with HIV and HHV-6. The quality and intensity of the anti-viral
cellular immune responses
can be assessed using lymphocyte subset analyses, natural killer cell mediated
cytotoxicity, and
measurements of cytokine production including IL2, IL4, interferon, etc. The
composition of the viral
proteins that act as targets for antibody and cellular immunity can be deduced
from a knowledge of
the nucleic acid sequences that comprise the virus genome.
Tissue culture methods can provide conclusive evidence of active infection by
cytopathic
viruses, as well as provide the viral isolate for susceptibility studies to
anti-viral agents. The
appearance of the CPE and the susceptibility of various cell types to the CPE
can be used as
distinguishing criteria in the identification of different types of viruses.
As noted above, several types
of viruses induce cellular damage through the induction of apoptosis. This is
seen morphologically
as cellular shrinkage and progressive~degeneration. Some viruses tend to cause
cellular enlargement,
rather than shrinkage. A cause of cellular swelling can be disruption of
mitochondria) catabolism of
lipids, yielding foamy vacuolated cells. Infected cells can fuse with each
other yielding cell syncytia.
In general, once a CPE has begun it will progress throughout the culture. With
many viruses,
however, only certain cell types will display the CPE. For example, human
cytomegalovirus (HCMV)
will grow in human but not in animal fibroblasts, and not very well in human
epithelial cells. The
major limitation of tissue culture techniques has been the apparent failure of
routine viral cultures to
detect the types of viruses to be described in more detail in this
application.
Molecular probes: Virus infection can also be inferred from the results of
molecular probe
based assays. The complimentarity between the nucleotide sequences of a
molecular probe and a
target nucleic acid results in binding of the probe to the target. Moreover,
either through the addition
of nucleic acid synthesizing enzymes (polymerises) or simple reliance on the
viruses own replicating
enzymes, a complex of probe with a target sequence can elicit a synthetic
reaction such that the probe
is extended from its 3' end with a sequence that is fully complimentary to the
part of the target
sequence adjacent to the site of initial binding by the probe. This feature
has formed the basis of a
recycling DNA synthetic technique termed the polymerise chain reaction (PCR).
PCR refers to
enzymatic amplification of a defined DNA sequence. It requires the following
reactants: target DNA
containing a known sequence to be amplified; oligonucleotide primers
complimentary to the flanking
regions, on opposing DNA strands, of the particular segment of double stranded
DNA to be
replicated; DNA polymerise enzyme; deoxynucleotide triphosphates (dNTP) and
buffer. The PCR
is performed in a thermal cycling machine. PCR proceeds by denaturing the
double stranded DNA
molecule by heat; and cooling in the presence of the oligonucleotide primers.
Because of their high
*rB
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concentration and greater mobility in solution, the primers bind more rapidly
to the target DNA than
the slower reannealing process exhibited by the larger complimentary DNA
strands. The primer DNA
complex provides a substrate for DNA polymerise. In the presence of dNTP, the
polymerise will
extend the primers in a DNA synthesis reaction. Each newly synthesized strand
will be complimentary
to the template DNA and will acquire at its 3' end, the sequence complimentary
to the other primer
used in the PCR. On repeating, the newly formed hybrids will denature, thereby
providing two
additional template molecules during the next primer annealing step. With each
successive cycle of
heating, primer annealing and primer extension, there will be an exponential
increase in the targeted
segment of DNA. Eventually, the reaction will become rate limiting due mainly
to competition
between primer binding and reannealing of the greatly amplified single DNA
molecules synthesized
during the PCR. in a typical reaction, however, amplification in the order of
105 fold can be achieved
in from 25-30 cycles. The specifically amplified PCR product will be of
uniform size corresponding
to the distance separating the 5' ends of the two primer binding sites on the
opposing strands of the
target segment of DNA. 1t can be identified by electrophoresis in agarose gels
and further
characterized by a hybridization reaction using a labeled probe reactive with
the amplified sequence.
For RNA viruses, an initial reverse transcriptase reaction can be performed to
convert the RNA to
a DNA sequence. The single stranded DNA is replicated to a double stranded
molecule which is then
amplified by PCR.
Either PCR derived products or synthetic oligonucleotides can be used directly
to
determine the presence of a viral sequence in clinical material. Various
approaches have been used
to detect the binding {hybridization) of the probe to its corresponding viral
sequence. The major
limitation of molecular approaches, including PCR and direct probe based
assays, to virus diagnosis,
is the requirement to know at least some of the actual sequence of the virus.
This issue can, however,
be addressed by using conditions that favor the binding of probes that only
partially match their
target. PCR products generated in such low stringency reactions will reflect
actual sequences of the
bound target. By sequencing the PCR products, information can be obtained that
will allow for the
design of highly specific primer sets.
C. Utility of Nucleic Acid Sequence Information Obtained on Viruses
Sequence information on a virus can provide a wealth of useful information way
beyond the
design of specific PCR primers for diagnostic purposes. The sequences can
predict the actual
proteins that are encoded by the virus. Such proteins can be synthesized for
use as antigens to assess
anti-viral immune responses, and to evoke protective immune responses through
immunizations.
Antibodies that are formed through infection or by experimental immunization,
can also be used to
detect the specific virus. Protein data can help determine how a particular
virus is able to mediate
CPE in tissues and in tissue cultures. Relatively little efforts are directed
towards sequencing of
individual viral isolates from patients, because of the general assumption
that all viruses within a
particular category are essentially identical. As will be disclosed below,
novel sequence information,
especially on previously unrecognized viruses, can provide important new
insights into basic
molecular mechanisms of viral pathogenesis. In particular, it can help explain
how some disease
causing viruses have successfully evaded confrontation with the cellular
immune system.
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D. Viruses as a Potential Cause of Common Non-Inflammatory Diseases
In spite of advances in understanding the molecular nature of viruses, and
widespread
availability of sophisticated viral diagnostic techniques, little regard has
been given by others to the
possible role of viruses in non-inflammatory illnesses affecting humans and
animals. An appreciation,
by the inventor, of the existence of previously unrecognized "stealth virus"
infections has opened
many opportunities to pursue important avenues of clinical and basic research.
Although, the
information provided in this disclosure is primarily directed towards methods
of obtaining and
utilizing nucleic acid sequence data from various stealth viral isolates, it
is likely that the basic
concepts will drastically change the approach that clinicians will take to
human diseases. Areas of
special concern include viral induced brain damage presenting as psychiatric
symptoms in adults,
learning and behavioral disorders in children and dementia in the elderly. As
will be described, the
issue of viruses as a cause of common cancers will need to be reopened. The
significance of the work
also extends to potential contamination of blood and other biological
products, transmission of
diseases between humans and between humans and animals, possible contamination
of foods and
other environmental sources. It disclosing the invention it is appropriate to
begin with a general
overview of stealth viruses. review the established culture methods for these
viruses and then address
the main topic of this application, which is obtaining and using nucleic acid
sequence information on
these viruses.
Disclosure of Invention
Stealth Adaptation of Viruses as a Means to Evade the Immune System. A major
function of the cellular immune system is to recognize and respond to virus
infections. A successful
immune response can eradicate foreign viruses by destroying infected cells
prior to the release of
progeny viruses. Symptoms of an acute cytopathic virus infection commonly
occur during the time
period required to generate a primary cellular immune response, and can also
be a byproduct of
cellular immune damage inflicted on viral infected cells. Unusually severe
infections can occur if the
immune system is impaired, for example, as a result of immaturity,
chemotherapy, coincident
infection with human immunodeficiency virus (HIV), or specific genetic
deficits in immune
competence. Certain viruses may also interfere with immunological defenses
through such
mechanisms as downregulation of the expression of histocompatibility antigens,
induction of
immunosuppressive cv_ tokines and related virokines, and by remaining
inactive, as in latent
infections.
Stealth adaptation was originally proposed by the inventor as a distinct
process whereby a
virus could remain actively cvtopathic in the absence of an accompanying
inflammatory cellular
immune response. Based on histological findings on brain biopsies, and on
repeated isolations of
atypically structured cytopathic viruses, it was suggested that these viruses
lacked critical genes
encoding effective targets for the cellular immune system. This original
hypothesis is still foreign to
most virologists who intuitively believe, either that all viruses possess
ample targets for immune
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recognition and/or that viruses without such critical elements would be unable
to replicate, cause cell
damage or pass between individuals.
Stealth viruses were defined as cytopathic viruses able to establish a
persistent infection
because of deletion and/or mutation of specific genes, which, if present,
would code for immunogenic
components able to evoke an effective anti-viral cellular immune response. The
existence of stealth
viruses is best understood within the framework of varying strategies used by
viruses to evade
immune elimination. Essentially, the basic postulates to explain stealth
viruses are: i) That relatively
few viral components serve as major immunologic targets (epitopes) for T cell
recognition of infected
cells; and ii) deletion and/or mutation of the genes coding these immunogenic
epitopes can yield
pathogenic viral variants (stealth viruses) that strategically avoid
confrontation with the body's cellular
immune defenses.
The definition of stealth viruses does not follow the usual approach of
defining specific
molecular and morphological characteristics. Thus, as described in the
"Background Art" section,
the usual classification of viruses begins with the distinction between DNA
and RNA genome. Other
characteristics include single stranded or double stranded nucleic acid,
polarity of single stranded
RNA viruses, mode of viral replication, size and shape of the virion, and
whether the virus is
enveloped. The approach taken to initially define stealth viruses was based on
the appearance of a
fairly characteristic vacuolating, foamy cell appearing CPE in culture along
with the exclusion of
other known viruses. As the work progressed, several individual stealth viral
isolates were defined
in terms of more conventional criteria, including their electron micrographic
appearance,
electrophoretic pattern of isolated viral DNA, partial sequencing and probable
origin. Even with the
best characterized of these stealth virus isolates, however, the strict
chemical and morphological
classification schemes fail to account for the microheterogeneity and sub-
genomic expression that is
observed. Moreover, the precise chemical features of one isolate do not
adequately encompass the
broader concept of a diverse group of cytopathic viruses in which deletion
and/or mutation of
normally immunogenic components has occurred. Stealth adaptation is viewed as
a mechanism to
facilitate persistent infection by structurallv_ losing the capacity to evoke
an effective anti-viral cellular
inflammatory response.
Given the above considerations, stealth viruses do not originate from a single
source. It is
likely that stealth adaptation can occur with all of the presently known human
herpesviruses and many
of the additional cytopathic viruses known to affect humans and animals. Viral
sources other than
herpesviruses are certainly not excluded. In fact, as viruses downsize and
simplify, their initial
distinguishing characteristics tend to become less important compared to their
common pathogenic
capacity of overtaxing the metabolic resources of a cell. The application of
DNA/RNA isolation and
cloning techniques, as provided for in this disclosure, should continue to
provide informative
sequence data on various stealth viral isolates to help define their
individual origins.
Tissue Culture Based Screening Methods for the Detection of Stealth Viruses.
Stealth
viruses can most easily be screened for using basic tissue culture techniques.
The viruses are identified
by their capacity to induce a CPE in tissue cultures. It is 'advantageous to
use a frozen-thawed extract
of peripheral blood mononuclear cells added to normal human fibroblasts. The
cells are monitored
for CPE, and in particular, the formation of enlarged, rounded, vacuolated
cells, that often form
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syncytia. An important observation is that the intensity of the CPE is
enhanced by regularly replacing
the medium in the tissue cultures, as a means to limit the accumulation of
viral inhibiting components.
The CPE can also be enhanced by the addition of 30% boiled supernatants of
HCMV infected
cultures, and/or by the inclusion of boiled or otherwise inactivated
preparations of various viral
vaccines, such as a commercial feline rhinotracheitis-calici-panieukopenia-
chlamydia psittaci vaccine
manufactured by BioCor inc. Omaha, Nebraska. As discussed below, it appears
that extraneous viral
and bacterial and cellular DNA can become incorporated into the viral
replicative process and
enhance stealth virus yields. Such additions, are contraindicated when the
goal is to obtain primary
sequence data on the clinical isolates. Stealth viruses can also be isolated
from tissue biopsies,
cerebrospinal fluid, semen, urine, throat swabs and feces.
The routine successful culturing of stealth viruses has provided valuable
insights into the wide
range of illnesses that can fit the pattern of a persisting viral infection.
White, the initial focus was on
patients with neuropsychiatric illnesses, including the chronic fatigue
syndrome (CFS), it became
apparent that very severe, and even fatal neurological illnesses, were
occurring in virus infected
patients. The unique susceptibility of the brain to stealth virus infections,
could be explained on the
basis of spatial segregation of the various functions of the brain. Thus
unlike other organs, limited
damage to the brain can not be compensated for by heightened activity
elsewhere. The induction of
malignancy provides another example where damage to even a single cell can
have dire consequences.
Evidence for stealth viruses has been obtained in a number of patients with
myelomas, melanomas,
brain tumors, lymphomas and breast cancers (see below). Stealth viruses have
also been cultured from
animals, including symptomatic pets of patients with neuropsychiatric and
oncogenic illnesses.
The finding of atypical cytopathic viruses in patients with such a diverse
array of clinical
findings has unfortunately tended to impede rather than accelerate scientific
acceptance of the basic
culture findings. This is one reason for again emphasizing the potential value
of actual sequence data
on cultured virus isolates. The combination of tissue culture and molecular
methods has provided
informative sequence data on several stealth virus isolates. Moreover,
recombinant clones resulting
from these studies have provided a useful set of reagents to pursue stealth
viral studies as well as
other research and commercial endeavors.
Obtaining Sequence Information on Stealth Viruses. Methods are in place such
that once
a stealth virus is cultured, one can readily proceed to defining its
composition. As described in the
"Modes for Carrying Out the Invention" this can be achieved using a variety of
molecular methods,
including PCR, primer induced nucleic acid synthesis, isolation of viral DNA
and/or RNA. The
nucleic acids can be sequenced and this information used to ascertain the
potential biological
properties of the viral isolate. Other approaches are also available including
amino acid sequencing
of protein products in culture supernatants and deriving, by reverse genetics,
the probable nucleotide
sequence of the coding gene. Cellular toxic products can also be isolated from
cultures and their
composition can be determined and related back to the genetic composition of
the virus. Of these
various approaches, the "Best Mode for Carrying Out the Invention" proceeds
from culturing a
stealth virus and determining its genetic sequence as described in the
following section.
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Modes for Carrying Out the Invention
The culturing of the stealth viruses comprises inoculating a test tube
containing human MRC-
S fibroblasts with a frozen-thawed aliquot of ficoll-paque isolated and washed
mononuclear cells
obtained from the equivalent of 4 mls of blood collected in an ACD (acid
citrate dextrose) anti-
coagulated blood sample. The MRC-5 cells are maintained in 5 mls of X-Vivo I S
serum free medium
(BioWhittaker, Walkersville Maryland, USA). The tubes are placed on a rotator
at 12 revolutions per
minute in a 37°C incubator. The cultures are observed daily for a CPE.
A positive culture is defined
as i) the loss of the following normal features of the cell monolayer. Normal
characteristics include
a monolayer consisting of an inconspicious sheet of elongated flat cells
without noticeable
intercellular gaps. The normal monolayer extends to the base of the test tube
without evidence of
cellular detachment. Similarly, the periphery of the normal monolayer should
have < 5% of cells
showing signs of rounding and/or enlargement. The monolayer should also not
display areas of
pigmentation or granularity. In addition to the loss of such normal features,
a typical positive culture
will show most of the following changes. The monolayer transforms to a rather
coarse interwoven
meshwork of readily apparent cells with intracellular retraction; evidence of
detachment of cells,
especially from the base and periphery, with scattered islands of reattached
cells. Parts of the
monolayer and the reattaching cells become foci of enlarged, rounded, or
distinctly abnormal
appearing cells, either alone or in apparent syncytia. Multiple areas of
increased pigmentation and/or
patches of residual cellular debris can be seen. An important feature of any
questionable culture is the
marked deterioration in the overall appearance of the culture and in
individual cells I 5-120 minutes
following replacement of the old media with fresh media. Signs of cellular
destruction, abundant lipid
accumulations, extraneous particulate matter, and formation of granular, rod
shaped and branching
structures can be observed over several days. Typically, the positive cultures
do not undergo the cell
shrinkage and disappearance seen in control cultures. Moreover, the CPE can be
transferred from a
positive culture by using a frozen-thawed extract of centrifuged cells,
detached by gentle vortexing
a positive culture. Secondary and tertiary cultures will typically show a more
subdued and focal
changes. Frequent, even daily refeeding, especially with media enhanced with
boiled supernatants of
human cytomegaloviral or other herpesviruses and even positive stealth
viruses, is sometimes a critical
element in maintaining strongly positive cultures. Typically a 30% addition of
boiled supernatant of
a human cytomegalovirus culture, is used for this purpose. Additional
confirmatory tests can include
positive immunofluorescence of infected cells using selected human sera, wide
range of permissive
cell types, and exclusion of intact conventional viruses using specific
antisera and molecular based
assays. One aspect of the molecular based confirmatory assays is the
generation of atypically sized
PCR products using various primer sets based on sequences of known
conventional viruses or on
known sequences of previously cultured stealth viruses. Sequence information
obtained on such
atypically sized PCR products, including products generated from reverse
transcribed RNA, can allow
for the design of additional PCR primers tailored for the specific stealth
virus being cultured. The
following information provides an outline of the approach taken. and describes
the results obtained
in the molecular analysis of a "Stealth Adapted African Green Monkey Simian
Cytomegalovirus"
Stealth Virus. The virus was originally isolated using culture methods from a
patient with chronic
fatigue syndrome. An aliquot was deposited at the American tye Culture
Collection ATCC and given
accession number VR2343. A culture was reestablished from a frozen aliquot of
an early passage and
grown on human fibroblasts, (BioWhittaker, Inc.. Walkersville. 1~1D.).
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PCR Products: The cultures were used to generate PCR products. Several primer
sets were initially
used. A set of primers, designated SK43 and SK44, based on the tax genes of
HTLV I and HTLV
II, respectively, yielded 2 products of approximately 1,500 bases and a
smaller product of 0.67 kb
bases.
DNA Extraction and Cloning. PCR products were isolated from agarose gels and
ligated into a
commercially available plasmid ( pBluescript, available from Stratagene, La
Jolla, CA). Purified DNA
was also extracted from the cultures, cut with a restriction enzyme, and
cloned into pBluescript. Two
independent experiments were performed on culture-derived DNA, yielding two
sets of cloned DNA.
An interesting observation was made during the work up phase for these
studies. Restriction enzyme
digestion of a conventionally structured virus is expected to yield equimolar
amounts of contiguous
fragments representing the entire genome. On agarose gel electrophoresis, the
digestion products
should be seen as multiple bands of essentially equal intensity. In contrast
to these expected findings,
electrophoresis of restriction enzyme digested DNA isolated from the stealth
virus cultures yielded
numerous bands of widely differing intensities. The uncut DNA migrated as a
band of approximately
20 kilobases (kb), yet the aggregate size of the bands following digestion
clearly exceeded 50 kb. The
PCR generated products and the products of enryme digestion were ligated into
pBluescript plasmids
and cloned.
Clones and Sequencing. The PCR clones were designated IS-5-2, 15-5-4 and
SK43/43. The 3B series
of clones was obtained using EcoRI digestion of DNA extracted from the
material, pelleted by
ultracentrifugation, that was present in filtered supernatants of infected MRC-
5 cells. The C16 series
of clones was obtained using SacI digestion of agarose banded DNA extracted
from the material,
pelleted by ultracentrifugation, present in filtered supernatant of lysed
virus-infected cells. The T3 and
T7 promoter sites of the pBluescript vector were used in sequencing reactions
to obtain partial
sequence data from the ends of each of the inserts. Extended sequences of the
inserts in selected
clones were obtained using primers based on the T3 and T7 readouts. The
sequencing services of the
BioServe Biotechnology, Laurel, MD, U.S. Biochemical, Cleveland, OH, City of
Hope Cancer
Center, Durate CA; Midland Certified Reagent Company, Midland, TX; and Lark
Technology,
Houston, TX, were used with excellent correlation of the occasional duplicate
and even triplicate
testing of the same clones. The individual sequences were analyzed against
GenBank entries using
the gapped BIastN and unfiltered BlastX programs of the National Center for
Biotechnology
Information (NCBI) of the National (.ibrary of Medicine. A "p" value of < a -
2.0 was used as a
cutoff for a significant nucleotide or amino acid sequence homology.
Results. The PCR product I 5-5-4 was t .5 kb bases in length and flanked by
the SK44 primer.
Sequencing of this product showed a statistical significant relatedness, by
both BIastN analysis, to a
portion ofthe human cytomegalovirus (HCMV) genome that codes a protein
designated UL34. The
15-5-2 product of a similar size and was also flanked by the SK44 primer. Its
internal sequence could
not, however, be matched to any known sequence. The 0.67 kb product was
flanked by the SK43
primer and when first examined had no significant matching with any GenBank
entry.
At least partial sequencing has also been obtained on over 300 clones from the
virus infected cultures.
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For many of the clones, the sequencing merely comprise a relatively short
readout from the T3 and
T7 promoter sites of the pBluescript plasmid. For selected clones, complete
(C) sequencing has been
obtained. As with the 15-5-4 PCR product, several of the clones contained
sequences that could be
statistically aligned by BlastN analysis to at least some portion of the
protein coding regions of the
HCMV genome. The BIastX program, which is based on the deduced amino acid
sequences coded
by a nucleotide sequence, identified many additional clones with significant
partial sequence
homology to various HCMV proteins. The matching was often incomplete with
apparent gaps and
occasional insertions in the sequences of the stealth virus clones. An overall
indication of the HCMV
proteins for which at least some portions could be aligned with a sequence
contained in one or more
of the stealth virus clones is shown in Table 1.
Table 1. HCMV Proteins Identified by Homology Searching Using Sequences in the
DNA
Extracted From Cultures of Stealth Virus-I
UL14 UL22 UL23 UL29UL31 UL32 UL34 UL35 UL36 UL37 UL38 UL40
UL41 UL42 UL43 UL44UL45 UL47 UL48 UL49 UL50 UL51 UL52 UL54 UL56
UL57 UL69 UL70 UL71UL72 UL75 UL76 UL77 UL78 UL84 UL85 UL86 UL87
UL88 UL89 UL93 UL95UL97 UL98 UL102 UL104
UL105
UL112
UL122
UL123
UL124
UL126UL130UL132 5 US18 US22 US23 US24 US25 US26
UL141 US21
UL144
UL14
US27 US28 US29 US30
* Greater than 5 clones matched to the proteins that are underlined and ten or
more clones
matched to the proteins highlighted by bold print.
Note: The genome of the fully sequenced, laboratory-adapted, AD169 strain of
HCMV comprises
235,000 nucleotides base pairs. The virus has two linear segments, designated
unique Ions (UL) and
unique short (US). Each segment is flanked by relatively small regions of
repetitive sequences. The
potential proteins coded by the UL and US regions are designated numerically,
and extend from
UL1-132 and US I-36. Additional potential open reading frames are present
within the repeat regions
that flank both the UL and US segments. Fresh clinical isolates of HCMV
contain some additional
protein coding sequences, designated UL 133-151, that are not present in the
laboratory adapted
AD 169 strain. Sequence comparisons of animal and human herpesviruses indicate
a greater
conservatism of the central core sequences from UL30 to UL 125, compared to
the sequences prior
to UL30 and beyond UL 135.
As shown in the above Table, the nucleotide and protein matching regions of
the
stealth virus are widely distributed throughout much of the central core
region of the HCMV genome
and in the later part of the US region. The matching sequences were not
uniformly distributed
through the central core region of the HCMV genome. For example of 300 clones,
10 or more clones
matched to the UL36, UL52, UL86 and US28 regions of the HCMV genome, while
other regions
were not represented by any of the clones from which sequence data have so far
been obtained.. The
homologue of the UL83 gene of HCMV was not represented in any of the sequenced
stealth virus
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11
clones. The UL83 lower matrix protein (pp65) which is the major target for
cytotoxic T cell mediated
immunity against HCMV (Wills MR, Canmichel AJ, Mynard K., et al. "The human
cytotoxic T-
lymphocyte response to cytomegalovirus is dominated by structural protein
pp65: frequency,
specificity, and T-cell receptor usage of pp65-specific CTL. J. Viroi. 70:
7569-79, 1996). This finding
is consistent with the underlying assumption concerning gene deletion as a
means for stealth adapted
viruses to bypass cellular immune defense mechanisms. Major deletions were
also seen in portions
of many of the proteins that were identified using the BlasiX program.
Moreover, many of the
deduced amino acid sequences were not included in analyses based on putative
open reading frames
(data not shown). .
To recapitulate the findings, the number of clones that matched to specific
regions of the
HCMV genome varied from a single clone to multiple clones. The regions of the
HCMV genome for
which > 5 clones contained statistically significant matching sequences by
BlastX analysis are
underlined in the Table. Regions of the HCMV genome in the vicinity of the
UL36, UL52, UL86 and
US28 gene product were each represented by 10 or more of the 300 analyzed
clones. Noticeably
absent were sequences of the major target for anti-HCMV cellular immunity
UL83, whereas 6 clones
were identified that matched to portions of the neighboring UL84. All of these
clones extended
forward towards the UL86 and UL87 gene products. In addition to apparent
absence of major
proteins, many of the proteins for which partial matching was seen, showed
major deletions when
compared with the corresponding protein in HCMV. Moreover, individual clones
that matched to
similar regions of the HCMV genome, often displayed minor sequence
differences, indicative of an
unstable viral genome. These differences occasionally disrupted the potential
of a contiguous
nucleotide sequences to provide a functional open reading frame. They also
could account for the
unequal distribution and surprisingly large number of products seen following
restriction enzyme
digestion of the DNA derived from the stealth virus cultures. Also of note,
the aggregate lengths of
the cloned stealth viral DNA sequences that match to non-overlapping regions
of the HCMV genome
exceeded 100 kb. Since, as mentioned above, the stealth virus DNA migrates in
agarose gels with a
size of only approximately 20 kb, it can be assumed that the genome consists
of multiple fragments,
rather than as an entire full length cytomegalovirai genome.
Limited nucleotide and amino acid sequence data are available for rhesus
cytomegalovinrs
(RhCMV). Several of these sequences con esponded to regions of the HCMV genome
which matched
to portions of the prototype stealth virus sequence. For these regions, it was
possible to compare the
relative relatedness of the stealth virus sequence with that of RhCMV and
HCMV. This analysis
showed a significantly higher homology of the stealth vines sequences to RhCMV
compared to
HCMV. A comparison of the p values seen when matching the nucleotide sequences
using BIastN
program and deduced amino acid sequences using BIastX program of the stealth
virus clones against
homologous regions of HCMV and RhCMV sequences are listed in Table 2.
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Table 2. Comparison of Relative Homology of Sequences Present in Various
Clones Derived
From a Stealth Virus Culture to Corresponding Sequences in Human and Rhesus
Cytomegaloviruses Analyzed Using BlastN and BIastX Programs
Clone Region of BlastN Analysis BIastX Analysis
Homology HCMV RhCMV HCMV RhCMV
C16289.T3UL31 NS 9e-21 2e-41 8e-53
C16292.T7UL45 NS Se-04 2e-26 le-33
3B51.T7 UL47 NS 6e-13 Se-25 6e-38
3B642.C UL48 NS NS NS 9e-26
C16169.T7UL54 Se-07 4e-44 2e-42 2e-50
3B529.C UL71 Se-12 8e-23 Se-09 le-14
3B559.T3 UL76 NS 3e-15 4e-11 3e-26
3B13.T7 UL87 NS e-104 2e-83 e-102
C16123.T7UL89 Se-51 e-113 7e-84 2e-89
C16145.T7UL105 NS le-OS le-13 3e-i6
3B546.C UL123 7e-09 le-71 8e-28 3e-61
C162113.T3US21 NS NS 2e-61 8e-27
3B656.T7 US22 NS 7e-09 8e-28 3e-6l
The higher homology to RhCMV compared to HCMV identified the stealth virus as
not of
HCMV origin. The variable statistical levels of the matching clearly
distinguishes the stealth virus
from RhCMV. Complete identity over a stretch of hundred or more bases will
typically yield p values
of < e- I 00.
Very limited genetic information is currently available for other primate
cytomegafoviruses.
There are, however, several sequences in GenBank for African green monkey
simian cytomegalovirus
(SCMV). This provided an opportunity to directly compare a stealth virus
sequence with several
cytomegaloviruses. A much greater homology was seen with SCMV than for any
other
cytomegalovirus. Sequence data supporting the unequivocal origin of the
stealth virus from is
provided by comparing the sequence of the immediate-early gene transcriptional
unit of SCMV with
that of stealth virus clone 3B546 (Table 3). Several small gaps had to be
placed in the stealth virus
sequence for a proper alignment. The extraordinary high degree of homology
between the stealth
virus and regions of the SCMV genome, with p values often reaching zero,
unequivocally identified
the virus as a derivative of SCMV.
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13
Table 3. Comparison of Sequence of Clone 3B546 Derived from a Stealth Virus
With the Sequence of the Immediate Early IE 94 Transcriptional Unit of SCMV
Stealth Virus Sequence SCMV Sequence Nucleotide Identity p Value
1 - 421 8410 - 7984 408/428 0.0
408 - 930 7986 - 7464 504/525 0.0
929 - 4193 7435 - 4168 3085/3272 0.0
4 i 85 - 4360 3985 - 3880 259/297 3e-95
4496 - 4853 3707 - 3347 510/536 0.0
5046 - 5333 . 2941 - 2654 263/288 e-I 11
5394 - 6026 2557 - 1925 594/633 0.0
6043 7926 1893 - 11 1782/ 1884 0.0
The overall alignment of the two sequences required that variable sized gaps
be present
between the above listed matching segments. The size of the gaps for SCMV were
larger than those
for the stealth virus, consistent with other indications of genetic deletions.
Most of the additional
sequences deleted from the stealth virus were in non-coding areas, including
introns, known to exist
within the SCMV lE gene. Highly significant matching to two other regions of
the SCMV genome
was also present.
The identification of an SCMV-derived stealth virus was not an isolated
finding. Indeed, a
young woman with a prior history of bi-polar psychiatric illness was admitted
to hospital because of
coma and seizures. Although her cerebrospinal fluid was essentially non-
inflammatory, it grew out
an atypical virus showing extensive molecular cross-reactivity in PCR and
direct probe-based assays
as did the viral isolate from the CFS patient. Yet by culture, the wide host
range of permissive cells,
and the formation of vacuolated foamy syncytia, clearly distinguished the
stealth viruses from the
standard Colburn laboratory strain of SCMV. Such differences should be
reflected in the nucleotide
sequences of the viruses. Consistent with this conclusion was the fact that
while SCMV had clearly
contributed multiple genetic sequences to the stealth virus, other regions of
the virus could not be
aligned to known herpesvirai sequences. The virus DNA appeared to comprise
multiple fragments
with stretches of herpesviral-derived DNA, adjacent to sequences of uncertain
origin. The virus also
exhibited considerable sequence micro-heterogeneity. Similar stretches of the
viral genome often
showed multiple deletions. additions, substitutions and duplications. Sequence
heterogeneity was
confirmed in stretches of the genome in which genetic recombination had
clearly occurred.
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The possibility of cellular sequences contributing to portions of the
prototype stealth virus
genome was suggested by the significant partial homology (p < 0.05) of a
portion of one of the viral
DNA-derived clones to a cellular gene. With the ever increasing database of
cellular sequences and
the recent introduction of a "gapped" BlastN program, redoing the original
analysis has provided
many additional examples of cellular-derived sequences within the cloned DNA
from the stealth virus
culture. For example, the SK43/43 derived PCR product matches closely to a
cellular gene in the
Xp22 166-169 region of the human genome (GenBank accession AC005145) with a p
value of 0Ø
Other examples of clones from the SCMV-derived stealth virus culture
containing cellular related
sequences are provided in Table 4.
Tale 4 Regions of Homolog~r of Stealth Virus Associated Sequences with
Cellular Genes
Stealth Region of Cellular genes) Number of p value
virus clone with
clone numbermatching to maximum homology matching
cell
sequence (GenBank accessionnucleotides
(No. ofbases)(*reiterated sequence)
C1629.T3 124-345 AA570230* 98/111 1 e-20
(512)
C I 629.T7 25-76 Z97200* 50/52 I e- I 5
(410)
C16261.T3 51 l-534 N529i4 26/27 5 e-04
(676)
C16261.T7 97-119 AC002480 21/21 4 e-03
(536)
C 16242.T3 388-413 AL008718* 29/29 3 e-08
(620)
C 16242.T7 None detected
(563)
C16145.T3 335-361 AA535872 27/27 I e-OS
(U27784) (561 )
C16145 T7 None detected**
(U27938) (528)
*rB
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* Reiterated sequence were present in multiple copies within the cellular
gene. Most of the matching
sequences were also repetitive with the BlastN program identifying somewhat
similar sequences in
multiple cellular genes.
** Partial homology to human CMV is present. Specifically, 81 of the first 95
bases match to human
cytomegalovirus (GenBank accession number X17403) at position 153,273 to
153,367 (p=1 e-12)
The presence of rearranged, mutated, cellular sequences in stealth viral
cultures is
corroborated by the sequences present in various PCR products generated using
the same set of
SK43/SK44 primers in stealth virus cultures from three additional patients.
Multiple distinct products
were generated from each of the patients. Sequencing of the products showed
variable patterns of
incorporation of the different primers. Several of the products were
identifiable on the basis of Blast
analysis as being of cellular origin Table 5 .
Table S Matching to Cellular Sequences of Cloned PCR Products Amplified From
Stealth Viral
Cultures of Additional Patients Usins~ the SK43/SK44 Primers
Patient SK primers) Number of BLASTN homology to cellular gene
Clone No. incorporated* bases GenBank accession, Nucleotide match, p value
sequenced
Patient LB
LB.43 43/44 507 AA429618 175/189 1 e-66
AA429619 104/115 4 e-32
AA429619 89/90 4 e-22
Patient KE
C1113.T3 43 211 AA429618 162/176 S e-57
C1113.T7 44 280 AA429619 37/38 2 e-10
C 1123.T3 44 207 None identified
C1123.T7 43 216 AF027598 63/b9 1 e-16
C 1 ! 32.T3 43 21 ? None identified
C 1132.T7 44 272 None identified
C1142.T3 43 246 AC002377 48/53 2 e-09
C 1142.T7 44 275 AC003 I OS 31 /31 3 e-08
C 1 ! S 1.T3 43 228 282216 122/ 133 7 e-43
C 11 S I .T7 44 236 282250 127/ 144 5 e-25
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16
C 1 I 63.T3 43 131 None identified
C1163.T7 44 2l6 None identified
Patient TR
C 1311.T3 43 299 None identified
C1311.T7 44 227 None identified
C 13 I 43 205 AF027598 63/69 1 e-17
3.T3
C1313.T7 44 171 None identified
C 1322.T3 44 165 None identified
C I 322.T743 89 AA429618 26/26 5 e-06
C1325.T3 44 182 073168 100/105 3 e-38
C 1325.T7 43 158 None identified
C1333.T3 44 169 247066 82/94 3 e-16
C1333.T7 43 161 None identified
C 1334.T3 44 185 None identified
C1334.T7 43 164 None identified
C1335.T3 43 138 M32672 33/36 2 e-04
C1335.T7 44 236 AC003015 31/31 2 e-08
*Slight differences were occasionally noted in the primer sequences. Selection
for minor variations
in primer sequence has been previously noted in performing PCR assays with
these primers.
Additional primer sets that have been used to generate PCR products in various
stealth virus
cultures. Some of the more successful primers have been based on internal
sequences of various
clones obtained from the stealth virus culture. An initial indication of a
potentially successful primer
is based is heightened synthesis of RNA and/or DNA when the primer is added
directly to an extract
of a stealth virus culture. Synthesis is presumably being induced by a viral
or activated cellular
polymerise. Additional synthesis can be induced by the addition of DNA and RNA
dependent
polymerises. The importance of RNA dependent DNA polymerise was highlighted in
a series of PCR
assays performed on a stealth virus culture from a nurse with CFS. No products
were seen using the
regular PCR format, yet multiple distinct products were seen if an initial
reverse transcriptase reaction
was performed. This finding indicated that the template to which the primer
was binding was RNA.
The actual sequences used in this study were based on several clones that
contained commonly
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occurring regions of homology to HCMV, and subsequently shown to be even more
akin to
sequences of RhCMV. The sequences are shown in Table 6.
Table 5. Primers Based on Sequences of Cloned Regions of Stealth Virus-1 Used
to Amplify
Products by Reverse Transcription Followed by PCR From Positive Stealth Virus
Culture From the
Cerebrospinal Fluid of a Nurse With a Chronic Fatigue Syndrome Like
Neurological Illness
GenBank Plasmid Size of PCR product Primer sequence
accession No. designation with stealth virus-1
027952 C 162114 279 by 5'-AACCATGTCTGCCACATCG-3'
5'-CAATAGGATCTCTCGCGCAC-3'
027916 38647 373 by 5'-CGCTGTCGCTCTCTTCCTT-3'
5'-GAGCACGATACGGTGTTGC-3'
027888 38412 374 by 5'-CCTGTTGTCATCTTGTTCAGG-3'
5'-AATGTTCGACAGTCTGCGC-3'
PCR assays were initially performed on DNA extracted From the patient's
cultures with DNA
from an SCMV culture serving as a positive control. Each of the primer sets
tested gave negative
results when tested on DNA extracted from the patient's positive culture. When
the same primers
were used in reverse transcriptase PCR (RT-PCR) assay on RNA extracted from
patient's culture,
clearly defined PCR products were generated. The PCR product generated with
the primer set based
on plasmid C1621 14 was similar in size to the 278 base pair (bp) product
expected for stealth virus-1.
This primer set yielded a similarly sized, but faint product with SCMV. The
primer sct based on
piasmid 8614 wives a similar size product with SCMV and stealth virus-1 of 279
bp. A distinctly
larger product than seen with SCMV was generated using the patient's culture
(480 by compared to
373 bp). Multiple additional faint bands were also eenerated. The primer set
based on plasmid 3B412,
generated two products (550 by and a less intense band of 425 bp). Both of
these products were
considerably larLer than the product seen with SCMV or predicted for stealth
virus-1 ( 374 bp).
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18
Renewed interest in pursuing cellular as well as viral sequences in stealth
viruses was
prompted by the realization that certain stealth viruses could potentially
assimilate and transmit genes
able to transform cells. A search was, therefore, made for any cellular
sequences related to known
oncogenes. Preliminary indications for this were found with sequences obtained
from certain stealth
virus cultures and confirmed by additional sequencing of the SCMV-derived
prototype stealth virus.
Specifically the sequence data show that parts of the virus has acquired
several copies of a
gene with a deduced amino acid sequence closely related to that of the
oncogene termed melanoma
growth stimulatory activity (MGSA/GRO-alpha) chemokine . Please note that this
specific example
was not included in the application for which priority is requested. The
concept and prediction of this
finding was, however, expressed. The 3B516 clone was fully sequenced during
1998.
The ends of Eve partially sequenced clones matched by BlastX analysis to the
MGSA/GRO-
alpha and to other closely related chemokine proteins. One of the clones,
3B516, was completely
sequenced. It comprised 5,820 nucleotides. Except for matches to the other
four clones from the
stealth virus cultures (3B33, 3B624, 3B654 and 3B675), BlastN did not reveal
significant homologies
with current GenBank entries. By BlastX analysis, however, the nucleotide
sequence from the left
side of the clone could be translated into a string of proteins with highly
significant homologies to the
ULl4l, UL144, and UL145 proteins respectively of the Toledo strain of HCMV. An
apparent open
reading frame (ORF) was situated slightly beyond the region coding for the
UL145 protein. The
deduced amino acid sequence of this ORF failed to show a statistically
significant match to any
protein entries on GenBank. It did, however, show a weak partial matching to a
human cadherin
tumor suppressor protein. The right side of the clone contained three discrete
regions, each of which
could be translated into proteins that matched to MGSA/GRO-alpha chemokine.
Two of the matches
were statistically highly significant. Another potential open reading frame
was situated between the
region of clone 3B516 that showed a weak homology to the cadherin tumor
suppressor protein and
the region showing an identified, but statistically insignificant, homology to
the MGSA/GRO-alpha
chemokine. BIastX analysis matched this region to a human alpha chemokine that
is only distantly
related to the MGSA/GRO-alpha chemokine. The BlastX results indicating the
best matching proteins
for the various regions of clone 3B516, are summarized in Table 7. The Table
also shows the percent
identity and calculated "p" value for the HCMV matching sequences.
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WO 99/34019 ~ 9 PCT/US98/27744
Table 7. Proteins that Most Closely Match to the Deduced Amino Acid Sequences
Coded by Clone 38516 Using BlastX Analysis.
Nucleotide Matc hing Se uence
Restion Gene Accession Identity
# I value
970-1, 884 _ i 1167926 127/305 l e-59
HCMV UL 141
2,231-2.268 HCMV UL144 11167929 54/146 3e-18
3,122-3.361 HCMV UL145 11167930 52180 ie-22
3,584..4,015 cadherin-related tumor 014097 23/85 0.23
su ressor
4,095-4,343 al ha chemokine human 0586 31/83 0.015
4,583-4,807 GRO human P09341 28175 1.5
4,938-5,198 53/87 8e-23
5,469-5.795 45/109
Se-09
The deduced amino acid sequences of the potential ORF that comprised the 4
regions of clone 38516
that matched to a cellular chemokine gene, are shown in Table 8. The sequences
differ significantly
from each other, and to varying degrees, from the amino acid sequence of the
MGSA/GRO-alpha
precursor protein. Also shown for comparison is the amino acid sequence of the
closely related alpha
chemokine, macrophage inflammatory protein-2-alpha (Gro-beta). The alignments
for 3 of the
sequences were obtained from the BlastX program. The amino acids that match to
those of the
MGSA/GRO-alpha precursor protein are underlined. The cystines involved in
disulphide bond
formation are indicated with an asterisk. Sequence 2 contained an apparent
insert that separated two
closely matching segments. This insert is shown beneath the site separating
the matching segments.
The initial codon for this insert was a stop codon indicated by the # symbol.
The 4'" sequence did not
match to MGSAIGRO-alpha, but rather, as noted in Table 7, to a more distantly
related human alpha-
chemokine.
The sequence analysis shown in Tables 7 and Table 8, is consistent with a
genetic
recombination between a portion of the SCMV-derived stealth virus that encodes
several
eytomegalovirus related proteins and a region of the cellular genome that
encodes a protein with
chemokine activity. The data emphasize the value of obtaining sequence data on
stealth virus isolates,
and the potential that exists for stealth viruses to transmit potential
oncogenes.
CA 02282858 1999-08-24
WO 99/34019 2~ PCTNS98/27744
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CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
21
It is unlikely that the chemokine genes were present in the original SCMV from
which the
stealth virus was derived. The HCMV Toledo strain in which the UL144 and UL145
coding genes
have been sequenced, continues with sequential genes that code for proteins
designated UL146 to
UL 148. While the UL 147 proteins of both the Toledo and Towne strains of HCMV
do show weak
and statistically insignificant (p value 0.15), homology to an alpha chemokine
of guinea pig origin by
BlastX analysis, the common sequences show very little overlap with those
coded by the 38516
clone. Moreover, this would not account for the multiple copies of the human
chemokine related
sequences in the stealth virus. Additional differences between the stealth
virus and HCMV clinical
isolates include the lack of UL142 and UL143 genes. Further clarification of
this important issue
should be forthcoming from sequencing studies on SCMV isolates.
The previously alluded to genetic instability of stealth virus-1 genome may
account for
differences seen in the 4 regions of clone 38516 that matched, by BlastX
analysis, to the
MGSA/GRO-alpha chemokine. One of the regions clearly has a major insert, while
all have apparent
deletions. Slightly less statistically significant amino acid matching of two
of the regions occurred
with macrophage inflammatory protein-2-alpha chemokine, also known as GRO-
beta. This was not
unexpected since, as shown in Table 8, there is a strong homology between this
protein and the
MGSA/GRO-alpha chemokine. Other members of the superfamily include macrophage
inflammatory
protein-2-beta (GRO-gamma), neutrophil activating peptide/IL8, platelet factor-
4, beta
thromboglobulin and interferon-inducible protein- I 0.
The human MGSA/GRO-alpha chemokine gene has been more extensively studied than
the
other chemokines because of its possible role in the autocrine stimulation of
melanoma cell growth.
The 1,895 nucleotide MGSA/GRO-alpha gene comprises a 5' non-coding region
containing NF-
kappaB, HMG(1)Y, IUR, and Spl binding sites. It has 4 exons and 3 introns. The
first exon codes
a signal peptide (nucleotide 130-229) while the second, third and fourth exons
comprise the mature
protein (nucleotides 330...451; 565...648, 1 l 80- I 195). A long non-coding
3' end extends from
nucleotides 1196 to 1895. cDNA sequences of the MGSA/GRO-beta and MGSA/GRO-
gamma
genes show extensive homology with the mRNA sequence of the alpha gene. A
pseudogene has also
been identified with homology covering the 5' non-coding region, the first and
second exon and the
first intron of the MGSA/GRO-alpha gene.
The absence of intron sequences in the assimilated MGSA/GRO-alpha related
regions of clone
38516 indicates that the putative recombination event occurred at the level of
RNA, rather than at
the level of genomic DNA. The fidelity of replication by reverse transcription
is generally less than
DNA dependent replication. This may help explain the greater divergence seen
when comparing
nucleotide sequences than when comparing amino acid sequences. At the same
time, the apparent
amino acid conservation, especially with regards to the capacity to form
disulfide linkages (as
indicated in Table 8), suggests that the proteins are providing some positive
selective pressure. It has
not been established, however, that any of the chemokine related coding
sequences are being
transcribed and translated into functional proteins.
The patient from whom stealth virus-1 was isolated has not developed any
malignancies. As
discussed below, evidence for stealth viral infection has, however, been
obtained from a number of
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WO 99/34019 PCT/US98/27744
22
cancer patients and From several animals with various tumors. Useful
information should be
forthcoming from sequencing studies on stealth virus isolates from these
cancer patients.
Positive Stealth Virus Cultures in Cancer Patients
Multiple myeioma: Viral culture techniques were used to screen patients with
multiple myeloma for
stealth viruses. This inquirv_ was prompted by a woman who had previously
tested positive, as had
her son, informing me that her father had developed multiple myeloma. It
turned out that he had been
depressed for several years with many of the same symptoms experienced by his
daughter and
grandson. He tested strongly positive, as have over 100 additional patients.
On careful clinical review,
it is apparent that significant emotional and cognitive difficulties and sleep
impairment, are remarkably
common in patients with multiple myeloma.
Breast cancer: Several patients have had either their blood or tumor sample
tested
using the viral culture technique. Again, it has been surprisingly easy to
obtain positive, transmissible
CPE, from these patients.
Other cancers: The daughter of the multiple myeloma patient developed a
uterine
cancer. An medical office worker with a prior clinical~history of Lyme disease
developed a melanoma
on her finger. She, as well as her ill husband, gave strong positive stealth
virus cultures. Additional
stealth virus culture positive patients have developed lymphomas, brain
tumors, thyroid cancers,
salivary gland tumors, etc.
In addition to viral and cellular sequences, the data on clones generated from
the prototype
SCMV-derived stealth virus indicate that the viral replicative process can
extend to the incorporation
of genes of bacterial origin. Indeed, there is good evidence for bacterial-
derived sequences in at least
8% of the DNA clones derived from stealth virus- I infected cells. As outlined
above, the inserts in
180 clones of the 3B series and in 120 clones of the C 16 series have been
partially or completely
sequenced. Of the 300 clones, the majority have at least a portion of their
overall sequence that is
homologous, by BIastN and/or by BlastX analysis, to the HCMV and/or SCMV
genome. Other
regions of the same clones and numerous additional clones, contain sequences
that do not correspond
to HCMV and/or to the limited known regions of the SCMV genome. Of these non-
matching clones,
24 contained sequences that by BlastX analysis, could be partially matched to
different protein
sequences of bacterial origin. An additional clone had a nucleotide sequence
that was similar to a
bacterial ribosomal gene complex. The bacterial nucleotide and protein
sequences that most closely
matched to the sequences contained in the various clones derived from the
stealth virus-1 infected
culture are summarized in Table 9. For many of the matches, additional
bacterial sequences were also
identified, usually comprising groups of functionally similar entities.
Several clones contained non-
overlapping nucleotide sequences that, when translated by the BIastX program,
could potentially
encode amino acid sequences that corresponded to portions of quite distinct
proteins, not known to
be coded by any contiguous set of genes in bacterial genomes, and in some
cases, seemingly derived
from widely divergent bacteria. For several clones, the matching with a
particular bacterial gene
occurred in discrete segments separated by variable size gaps. The degree of
identity and the
corresponding statistical "p" values for each of the matching segments are
shown in Table 9.
CA 02282858 1999-08-24
WO 99/34019 23 PCTNS98I27744
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CA 02282858 1999-08-24
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CA 02282858 1999-08-24
WO 99134019 26 PCTNS98/27744
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CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
27
The data presented in Table 9, indicate the existence of bacterial-related
sequences in cloned
DNA extracted from the stealth virus-1 infected culture. The diverse range of
bacterial species
identified using the BlastN and BIastX programs, argues strongly against the
bacterial DNA being
a contaminant of the cloning process. The high levels of identity also exclude
the possibility of
diverged herpesviral sequences being mistaken for bacterial sequences.
A flanking sequence in clone 38313 matched to the human C-C chemokine
receptor, which
in turn matches to the G-protein coupled receptor coded by the US28 gene of
HCMV. With this
possible exception, the demonstration of a viral sequence followed by a
bacterial sequence in the same
clone has yet to be documented. This can clearly be inferred, however, from
the information provided
in the Footnote to Table 9. Specifically, near identity was observed between a
stretch of clone 38313
and a sequence contained in clone C 16246 which aligned to the HCMV gene
coding the US28
protein. Moreover, additional regions of clone C16246 show a strong homology
with several HCMV
coded genes. Similarly, the limited overlap between clones 38513 and 38525 is
informative. Beyond
the overlapping region, clone 38525 shows highly significant matching to HCMV.
The overall
sequencing data are consistent with variable patterns of recombination between
various sequences
of viral, cellular and bacterial origins.
It could be argued that the bacterial sequences have, in fact, incorporated
viral sequences,
rather than the reverse. When dealing with obligate intracellular
microorganisms, the distinction
between virus and bacteria is somewhat irrelevant. This is especially so when
several of the functions
ascribed to the bacteria, are in fact, mediated by bacterial plasmids and/or
subgenomic insertion
elements. The predominance of virus-related sequences, and the lack of
bacterial structures seen on
detailed electron microscopy of stealth virus-1 cultures, strongly favor the
notion of a virus with
assimilated bacterial-related sequences. The term viteria is proposed for a
eukaryotic virus which has
incorporated genes of bacterial and/or bacterial plasmid origin.
Many of the matching bacterial sequences correspond to genes involved in
rather unique
energy generating and metabolic conversion reactions. Particularly, noteworthy
are sequences
contained in genes that participate in the transport, , activation and/or
synthesis of uncommon
metabolites. Given such a wide array of metabolic functions, it is conceivable
that viteria could
maintain a limited capacity to metabolize, and possibly even to replicate,
outside the confines of a cell.
Certain bacteria could derive a competitive advantage by being infected with a
viteria that
encode functionally useful genes. The improved metabolic performance of a
viteria infected bacteria,
(or an infected fungus), could facilitate transmission of the underlying virus
infection. Conversely,
some of the pathogenicity of stealth viruses for human and animal hosts, could
be mediated by toxic
byproducts of the various metabolic pathways encoded by the assimilated
bacterial genes. Toxic
products have been detected in blood, urine and cerebrospinal fluids of
stealth vinrs infected patients,
and also in the supernatants of stealth virus cultures (unpublished).
Supernatants from mixed bacterial
cultures, obtained from a stool sample of the patient from whom stealth virus-
1 was originally
isolated, also induced a vacuolating CPE in cell culture (unpublished). In
addition to oile or more
toxin, the supernatants contain a filterable cytopathic agent that can be
passed in tissue culture.
Molecular studies on this agent have yet to be performed.
*rB
CA 02282858 1999-08-24
WO 99/34019 28 PCT/US98/27744
The presence of bacterial-related gene sequences in the stealth virus-1
culture has relevance
to diagnostic microbiology. Positive PCR based assays, using primers reactive
with various bacterial
sequences, have been reported in patients with chronic fatigue syndrome, Gulf
war syndrome, chronic
Lyme disease, Alzheimer's disease, multiple sclerosis, arteriosclerosis and
other diseases. These
reports may reflect the presence of limited bacterial-related nucleotide
sequences contained within
an essentially viral pathogen. Minor differences in the ribosomal sequences of
bacterial species have
also ied investigators to use PCR to classify the postulated bacterial
pathogens that were presumably
being detected. The BIastX findings showed an even better matching of amino
acid sequences than
nucleotide sequences. Viteria encoded proteins might be expected, therefore,
to evoke antibodies that
could be misinterpreted as evidence for infection with conventional bacterial
pathogens.
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
29
industrial Applicability
The detection of nucleic acids in stealth virus infected cultures, and in
clinical materials
derived from stealth virus infected patients and animals, has provided new
insights into the molecular
heterogeneity and potential derivation of stealth viruses from both viral,
cellular and bacterial
sequences. The utilization of molecular based probing and genetic sequencing
expands upon the
capacity of culture based techniques to detect stealth viruses and provides a
method to distinguish
between stealth virus isolates. Sequence determination of a given stealth
virus can be useful in relating
abnormality in specific gene expression and the clinical disease
manifestations. For example, it is
expected that the stealth viruses isolated from patients with multiple myeloma
may have incorporated
and lead to aberrant expression of a B cell growth promoting cytokine such as
interleukin 6. This
possibility can be determined using the techniques outlined in this
application. The determination of
stealth virus-isolate specific sequences can be used epidemiologically to
trace disease transmission.
This approach can be applied to the stealth virus epidemic currently being
studied in patients in the
Mohave Valley. PCR based assays on patients' blood and CSF samples using
primers reactive with
previously isolated prototype stealth virus were clearly useful in documenting
infection in the patient
who died with a cerebral vasculitis, the comatose patient with a prior history
of a bi-polar illness and
in the health care worker in whom probing of her stealth virus culture for
atypical RNA sequences
yielded positive PCR results.
The application of this research extend well beyond the field of medical
diagnostics. To
address this area first, it has been extremely useful to perform stealth virus
cultures in patients
presenting with severe neurological illnesses of uncertain etioloiry. In
previously published papers and
in a clinical paper recently accepted for publications, the positive stealth
virus findings have prompted
clinicians to introduce anti-viral therapies, such as ganciclovir. An
extensive outbreak of stealth virus
associated illnesses was recorded within the Mohave Valley region of the
United States. The illnesses
in many of these patients began with a gastrointestinal disorder, possibly
transmitted via stealth virus
infected bacteria. Several adults have died with multi-system illnesses,
including signs of progressive
encephalopathy. An accepted publication describes a 7 year old boy from this
region in whom two
brain biopsies were performed. The biopsies showed marked vacuolization, not
unlike that seen with
brain diseases attributed to priors. Interestingly, for over 7 months, his
illness was simply attributed
to attention deficit, oppositional defiant behavior, etc. Even his parents,
both of whom are physicians,
failed for a long time to see signs of an organic illness. His MRI was grossly
abnormal, yet his clinical
neurological signs were initially quite minimal. He eventually became
clinically severely ill, being
unable to walk and suffering severe headaches. Yet the concept of a virus
encephalopathy was still
not considered by specialist neurologists, who favored a degenerative process.
Following the
successful culture of a stealth virus from brain and cerebrospinal fluid, the
child was beLUn on anti-
viral therapy 9ganciclovir). his downhill clinical course began to stabilize
within the second week of
treatment.
Multiple other patients, variously labeled as having chronic fatigue Gulf war
syndrome, Lyme
disease, amyelotrophic lateral sclerosis, schizophrenia, depression and
dementia, have been begun on
ganciclovir on the basis of a positive stealth virus culture. Ongoing studies
have also focussed on
patients with various malignancies, and on patients thought to have a prior
associated illness.
CA 02282858 1999-08-24
WO 99/34019 3~ PCT/US98/27744
The identification of a stealth virus infection will be aided by sequence
informarion pertaining
to the particular virus isolate. This will help remove subjective uncertainty
that can result from always
distinguishing a toxic effect from a viral cytopathic effect. It will help
define the origins and
composition of a particular isolate. It will help identify patterns of disease
transmission, for example
between family members and within a workplace environment. The possibility of
disease transmission
via blood and other biological products, and even in foods and from other
environmental sources can
be effectively explored when one has sequence data to help tag and quantitate
the virus.
Sequence data can also assist in understanding the replicative processes
employed by various
stealth virus isolates. While some viruses, may replicate primarily through a
DNA dependent DNA
polymerase, there is evidence for reverse transcription of RNA to DNA. This is
relevent to the content
model in which fragments of RNA are possibly being assembled on pieces of DNA
forming a type
of scaffold. Such speculations will be refined by knowledge of actual sequence
data. More
importantly, this model needs to be tested in terms of whether shorter pieces
of nucleic acids could
potentially disrupt the putative scaffold and lead to cessation of viral
replication.
The sequence data themselves are also useful since they relate to overall
functions of the
stealth viruses. This is seen particularly with the cellular and bacterial
sequences that can apparently
become assimilated into the viral replicative process. The sequence data can
also define antigenic
targets for potential antibody production, both as adjunct diagnostic agents
and as a possible means
to evoke in vivo protective antibodies that may prevent viruses entering the
brain.
While stealth adapted viruses are mainly being viewed as pathogenic agents,
they may also
find beneficial scientific and commercial uses as potent vectors for the
transfer of genetic information.
Both the viruses themselves and the various genes identified through
sequencing efforts on stealth
viruses, should find widespread applicability,, especially if species barriers
do not exist for at least
some of the isolates.
Finally, the discovery of stealth viruses and an understanding of their
sequence composition
has led to a series of publications, some of which have been summarized
earlier. A listing of the major
publication, including several that are "in press" is as follows:
Martin W.J. Detection of viral related sequences in CFS patients using the
polymerase chain
reaction.in "The Clinical and Scientific Basis of Myalgic Encephalomyelitis
Chronic Fatigue
Syndrome." Byron M. Hyde Editor. Nightingdale Research Foundation Press.
Ottawa Canada pp
278-283, 1992.
Martin W.J. Viral infection in CFS patients. in "The Clinical and Scientific
Basis of Myalgic
Encephalomyelitis Chronic Fatigue Syndrome." Byron M. Hyde Editor.
Nightingdale Research
Foundation Press. Ottawa Canada pp 325-327, 1992.
Martin WJ, Zeng LC, Ahmed K, Roy M. Cytomegalovinrs-related sequences in an
atypical cytopathic
virus repeatedly isolated from a patient with the chronic fatigue syndrome.
Am. J. Path. 145:
441-452, 1994.
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
31
Martin W.J. Stealth viruses as neuropathogens. College of American
Pathologist's publication "CAP
Today" 8 67-70, 1994
Martin WJ. Stealth virus isolated from an autistic child. J. Autism Dev. Dis.
25:223-224,1995.
Martin WJ, Ahmed KN, Zeng LC, Olsen J-C, Seward JG, Seehrai JS. African green
monkey origin
of the atypical cytopathic'stealth virus' isolated from a patient with chronic
fatigue syndrome. Clin.
Diag. Virol. 4: 93-I03, 1995.
Martin WJ, Glass RT. Acute encephalopathy induced in cats with a stealth vinrs
isolated from a
patient with chronic fatigue syndrome. Pathobiology 63: 115-118, 1995.
Martin WJ. Severe stealth virus encephalopathy following chronic fatigue
syndrome-like illness:
Clinical and histopathological features. Pathobiology 64: I-8, 1996.
Martin WJ. Stealth viral encephalopathy: Report of a fatal case complicated by
cerebral vascufitis.
Pathobiology 64:59-63, 1996.
Martin WJ. Simian cytomegalovirus-related stealth virus isolated from the
cerebrospinal fluid of a
patient with bipolar psychosis and acute encephalopathy. Pathobioiogy 64:64-
b6, 1996.
Gollard RP, Mayr A, Rice DA, Martin WJ. Herpesvirus-related sequences in
salivary gland tumors.
J. Exp. Clin. Can. Res. 15: 1-4, 1996.
Martin WJ. Genetic instability and fragmentation of a stealth viral genome.
Pathobiology 64:9-17,
1996.
Martin WJ, Anderson D: Stealth virus epidemic in the Mohave Valley. ! Initial
report of viral
isolation. Pathobioiogy 1997; 65:51-56.
Martin WJ: Detection of RNA Sequences in Cultures of a Stealth Virus Isolated
from the
Cerebrospinal Fluid of a Health Care Worker with Chronic Fatigue Syndrome.
Pathobiology
Martin WJ: Cellular sequences in stealth viruses. Pathobiology 1998;6b:53-58
Martin WJ: Bacteria related sequences in a simian cytomegalovirus-derived
stealth vinrs culture. Exp
Mol Path (in press).
Martin WJ: Melanoma Growth Stimulatory Activity (MGSA/GRO-alpha) Chemokine
Genes
Incorporated into an African Green Monkey Simian Cytomegalovirus (SCMV)-
Derived Stealth Vinrs.
Exp Mol Path (in press).
Martin WJ Anderson D. Stealth virus epidemic in the Mohave Valley: Severe
vacuolating
encephalopathy in a child presenting with a behavioral disorder. Exp Mol Path
(in press).
*rB
CA 02282858 1999-08-24
WO 99/34019 PCTNS98/27744
SEQUENCE LISTING
<110> Martin. W. John
<120> Stealth Virus Nucleic Acids and Related Methods
<130> CCID-2
<190> US
<141> 1998-12-29
<150> 09/001,189
<151> 1997-12-30
<160> 94
<170> PatentIn Ver. 2.0
<210> 1
<211> 2142
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<213> Stealth virus
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taaatattaa taacgaaatc atatgtaaaa aacaaaagca aaaaaataaa taattattat 290
tgcaacatct attgcatgat aatatgcatt cttagtccca tcaaatcatt catggggata 300
caagcatcta tttgtaattc atcactaaaa tgcatgtttt cttttctgca taatctaact 360
cttagtctta cttcgctaaa caagcctaaa aagttttgat aattgtttct aacatcttct 420
atttggactt ttaacaattc agcaatttta atcatttttt tacttttctt ctcgttttct 480
tatggttaaa actcctaagc ttgttaatct gttaactaaa gtttgataac taatttattt 590
ttcatagcct tcatgagaat aatctccaac ttttatttct tttcaaaaag atttgattgt 600
tgcatcatta acatttttga ttccgttagt tctattttta gaaacaattt gaatagcatt 660
ggtttttcta tttaaaaaat ctctaatatg gcttttgtat ctttgaatag atataattga 720
taaaccaact tttttagcaa tttgtcaatt actcaaattc attcaaggtg caattaattg 780
atagtttttt gtttgctttt tccaattttg ctggattaga acaaaaacta aatactaaat B40
caataaatac atcctatttt acaattataa atgtcaaatt gttttgtatt gaaggtatga 900
caaactattt tagaatttat atcccacttg ttatttctta ttacttttat attttaataa 960
tataataatt ttaataatat attttgattt ttatcagtag aatgaggtca ttaatatgac 1020
aaaagaaaac aaaactttaa atattctttt tattggggat attttttctg aagcaggaat 1080
tgaaatagtt gaaaaacatt taccttcttt aataaaagaa aataaaatcg atgttgttat 1140
agcgcaaagt gaaaatgttt caggaagaaa aggtttagtt aaaaaagatt atttaagact 1200
taaaaaagca ggtgttaata tttttacaat tggaaaccat gtttgagcta aagatggaat 1260
tttttcaata atcaataatc ctgaattagt tagacctgct aatatagatg aaggatatcc 1320
aggaaatgga tcaatagttt ataaatgtaa taatggaact actttaagag ttacttcatt 1380
aatgggaatt acttttaata aactattagc cccttgaact caagaatatg ccaataactt 1440
1
CA 02282858 1999-08-24
WO 99/34019 PCT1US98/Z7744
ttttgatact atagataaca tcattgaata tggagaaaaa actgattttc actttgttga 1500
ctttcacgct gaaacaacaa gcgaaaaata tgttttaggt ctttatttag atggcaaaat 1560
tgatggtatt tgtggcactc acacacatgt gcaaactaat gatgcacatg tgctacctaa 1620
ggggacttgt tatttaacag atgctggaat gagtgggcca tttgattgtg ctattggagc 1680
aaactttgat gaagtttatc aaaaaatgag atataacaag aatgttaaat tcattccttc 1740
aaaaaacaaa agccaattta atggtgctat attaaaacta aatagtgaca aaagccaaaa 1800
caaaattatt ccaattaaca taagacaaga ataaaaaatg atataactag ttcaagcttt 1860
acataggtaa agctgcaagt tagtcaaaga gcttggctat tagactaata tatgtgttac 1920
taatgaacaa gacaaatgtg cttgaatcaa tggaccaaca ttgagggtgt agactcttgc 1980
attgtatagt aagtgatttt aagtggtatt ctttaccgct atttttttac aatttattat 2040
aaaatttgca aagataaaaa agaaataaaa attatgaaat atccaaagtc ttttgttgat 2100
tttactaata ttgatgttga tttagaagct agtaatgaat tc 2142
<210> 2
<211> 854
<212> DNA
<213> Stealth virus
<400> 2
gaattctntn ntnnagaanc tcctcgcnng tgatgcgaat gttgcccgaa cactgccgat 60
cncacacact atgctcgtag atnaacggcn atcgncttcn cggaacnntg ncgcctngcn 120
nnatngncta tcaacanatt gcnanncttn gnnggcttng aggtangacg cggaatttgg 180
agcagtcccc gaacgggttt tggcgcgtac gcagcttccg taactatgca gactatgctg 240
ttgagtgcgc cgtttgccga cggacttgcc caactcaggg cgctaggaaa caaacaccgc 300
tgcgcaatca tgtgtgcaga ggctgtatgg tggcgctgtc atcggcggat catnacggac 360
tacctganca gccaaggcga aagcgtgatg cacatcctgg ggtcatcgna agtcaatgag 420
gccagcatga cgcctggagc tgtcatgaat ggggaaggtt taatttatcc agcccgaaag 480
tgatatacga nnaatagtgt tagtgatttc gtctcgaata ttagctttta ccccgctggc 540
ctgggtgtcc ggtttaccag catcttggcc ccagaaattg tgaatcgaag gaattaccat 600
tgcattccca cggaccacnn attggcntgn ttgcctttcc gangggngtt tgccgttccc 660
cgcnttttaa ttagtngggg cttaaaaact atttngnccc tgttttccna ccaaggtaan 720
tttaccaacc ccttttacct ttnaacaact ttcggggnaa taaggggccc taattgggnc 780
ntgntggggg ntncccnntt nggggggggt tgggcanttt ttttggggaa ttngngggac 840
caagggttgn aanc 859
<210> 3
<211> 809
<212> DNA
<213> Stealth virus
<900> 3
gaattccatc caggcttttg cttacagcct ggacttccag actcagctgc aaaagattcg 60
cgacctcaag gcacgctttg ccgatctgat taagcagcag catctcaacg cgtctgaaga 120
agtaccctta cccatgcccc acctaccagg aaacacggtc atngcctccc cgctgtcgtt 180
tgccaagggc ctggccgccc tagagaaata tgttttgggc ggntaccagt ggttaaccga 240
atgtatcaac cgtcaacctc tagtgtgtca acgcatagac gacattccgg ccgttttgcc 300
gtcaaccgat attgaccgca agagagtcgc cctagatcgc ctcaagcggn tgagttttag 360
tacaaagaac gaaatgtgtt acgaagttgt cgacgtattc ggnctccacc aactcatgtc 42C
2
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
caaaaatggc gttcccatac actttgnact gagctacgga aacgtgtttt tcaagtacat 480
ggcactacat cacgatgatn agcaattggc aaaaaaattt gcccaagtta aaaatttggt 590
gactggcagg atacaaagtg gtaacggtca atggtcgcnc gtancccaga ccttggaaaa 600
ccttctggtc ccaggatatt cccaatnccg aaccttnaaa ccccttactt ttcaggtcaa 660
aaccacttca ntanggtttn aagggaagaa aacttaacag tcttagtana acccttnaaa 720
aaatttttca nttttnatna tttggncggt aattcaagcc ctgggnaaac ttgggcaaan 780
tttgggaatg gtggcctttt naanggaaa 809
<210> 4
<211> 817
<212> DNA
<213> Stealth virus
<400> 4
gaattcggtg ttaaaatctt ttattttgat tataaaattg cgggagttaa aggcggttta 60
tattttcctt tattaactag tttgataatt tgcatattgg ttttatttat tagttgtcct 120
atttctttga gggttgcaat cttaataatt tatcgaaata aaaactataa agcttatcga 180
acatttaaat ttatggcttt aattttaagt gctttgcctt ctgttttata tggacttttt 240
ggtttagtac ctttgacttg aatgaacaaa aatatattta atatggaaaa tggaacaaac 300
ttatttaatg ccacaatggt cttaagttta atgtgcattc caactatggt caactcatta 360
ttattgcaat ttgaaaaagt tgatttatgt ctaaaactct caggtagtgc tattggttta 420
agcgaatcaa aagtaattta taaaataatt aaaaagtcat taaacaaaaa aatattttta 480
atttatatta gctcttttgc cagagttatc ggtgaatcag ctgctttaat gtttatttta 590
aatagcaata attattcaga aaattttaca aatattaaga aaatttttta actcttcatt 600
gcgtnctctt tcagtattta ttaatgctaa tttctttgct ggaaaatggt gggccgaatg 660
caaacctagg aagttaccat gtttaaattt aagctttttg gntcttatta aattngggga 720
ataacctttt aatttaaatg gctggcnaat tcattaattn atttggttaa attttcaaaa 780
aaggtccaaa aaaaaaccct taaannggan tttangc 817
<210> 5
<211> 834
<212> DNA
<213> Stealth virus
<400> 5
gaattctaga ttgatatttt ttagaatttg tttacctttt ttgttgtatc aaaagttaac 60
attttctaat ttaaaaattg tatttttttc catatttact cctaatgttt tctttttaat 120
ttgcttaatt ttggaatcac aaattctgat aatgataaga ggatagttat tgttacaaat 180
gacaccatag cacaatagta catagttgga attgagtaag ctgaaggcaa tgataattga 240
gcattcattc tagtcgttaa tgtttggcca aataataata agctaatatg ttttgaatta 300
cttagtccgc tagttaaaat aaatggtgtt gtttctgaaa agattttagc cagcattaaa 360
ataataatat ttaaaagatt aggccaaatt ttaggtaatt ttattttgaa taaaattgca 420
ctttcgctga gtcctaaagc agctgcacta gttactacac tttgatcaac tatttcaagg 480
agcttcttta attcagcgac agctaaaggc aaataacata acgctaattg ctaaagctcc 540
agctaaaagt gagttactgg ttttaccacc taaagccaat tggaaaagtt cctaaaaaga 600
tagctgaacc caaagacacc caaaaagatn aaaccaggcc attggaagtc attaacctgg 660
aaatggaagt ttattcaaaa taccttaaat tttgcttttt tttgcttttt ggttaaaatt 720
caacccaaaa ttaaattggt taccttaaaa aaaggccnaa aaaggggaaa ggtttaccta 780
3
CA 02282858 1999-08-24
WO 99/34019 PCTNS98/27744
aaaaattggc ttcctaaaag gaggattttt ttnaaggggg ttnaaaatna aagc 839
<210> 6
<211> 846
<212> DNA
<213> Stealth virus
<900> 6
atttnnnnnc ttgaannccc tngnctcaat cagtggacca ttaccgatgc gcaggggctt 60
gatacgacgg tgatgatctt caatctgcgt acgggtgtac gtttcaccga tgatatgttc 120
aagatcgact atcagcgcat cgcgatgaaa cgaaaaggtc agtaatagtc agcttagagc 180
ggttccagtt aaaattgaat cgttggattc gctctatctg cctgtttttg cgcgcatctt 240
atccgaaaac cgtttcacac ttttcgagat gcgctttagt tgctgcctga tgtttgcatt 300
ttttggataa atggttaggt tcgcgaccat cttttgatga ccgcgagtct ttttcccatg 360
accttttctg ttgctacctg gaacatcaat tccgttcgcc tgcgcatgcc gctggtcgag 920
cagttcttga gcgattatca gcctgatgtt ctgtgtctgc aggaaaccaa atgcccggac 980
gatcaattcc cttccaaggg ttttcgtgcg cttggttatg agcatatcgc gatcangtgg 590
tcagaagggc tatcatggcg ttgcaactat ttccaagcgc ccgctgannc gatgtcanan 600
aagtancggc ttttgcgaaa tgggcgactg ccgccatnct naagccgcgg tttgttttca 660
agccggcgac aanaaangct ncgtatccca ttaaatttcc tacngtnccc ttgtctgggc 720
cnnttgaatt gantcccggg gaccccgggt tnatttnaat ccccaaaaat tttggcgcca 780
ttaaancctc tggntttttt ctttggaagg gnaaaattgc ccaanccgaa attgtngggc 840
acgtaa 846
<210> 7
<211> 774
<212> DNA
<213> Stealth virus
<400> 7
gagctcctat taaagcattt atagaaaaag tgcgaagcgg ttttgcatag gataatgcga 60
aagaaaatag atagagcggt tccaacgact aagtcttaac ttgaaccgct ctgatattcg 120
ttcgccgcct taataatagg tatatgcggc caaacattgt tcactagcgt cagattacag 180
agccgttgct ctgtaatagc ttattaccat tgatcttaat ccagatcaaa tgtcgcgatg 290
acaggcacgt ggtccgaagg acgctcccag ccgcgcgcct nacgcagaat ttgcagctcc 300
ttcatatgag cttcgagatc agcagagccc cagatgtggt caagtctgcg accacggtca 360
gcggcgtccc aatccttggc gcgataactc caccatgtat aaatcttctg gtctgctgga 920
atgacctgac gcatcaanat cgnttccagc nacncttcac acgcagatct tccagcgttg 480
tggtctcaat ccggtgtgtg gctgacgatt cttgganaaa ngctgtttgt gcggaccagg 540
acattcgtnt ttttncnaag tggggcngcc gaataatttg atgattcgnc cccacccagg 600
gaatccggac cnnaaatttt cccnttcctt gcccttgttc ttgcccacca nattcncctt 660
cggctatttt tncnttcaag cgnaaaaaac cntangcctt taatgncgnc canaaattnt 720
ttgggnnatt ttaaatttac ccnggggttt ccnggtcttt aantnaancc gntc 779
<210> 8
<211> 1694
<212> DNA
<213> Stealth virus
4
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
<400> 8
gagctcggaa ttcataacgc tttttatgtt cgccacgatg atggtgctgc tgatgacggg 60
tcagcgcgtc ttcggcgtga tcggatttgt gggcacaatc gccgcacttc tgctctgggg 120
caaaggctcg ttcgagatgc cctacaatgc cacattcgcg gtgttgaatt ggtatccgct 180
cataaccgtg ccgttctttg tattcatggg ctatatgctg tcggaatccg gcatcgccag 290
caatctctat cgtatgttcc atgtgtggtt tggaggcatt cgcggcgggc tggccttggg 300
caccatcggc ctgatggtca tcatttcctg catgaacgga ttgagcgtcg ctggcatggc 360
aattggtgca accgtcgctc tgcctgaact tcttaagcgt ggttataaca aggttatggt 920
gacaggcgtc attcaggctg gcagttcact cggcattctg atcccaccaa gcgtagtgct 480
ggtactttac gccatgatcg cccgacagcc ggtcttgcag ctctggctgg caggcatcgg 540
cccaggcttg ctgatggcag cacttttcgc catctacatt tacatacgct gccgcataaa 600
tcccgagctt ggaccgacct tgcccaagga agagctggaa cggattacct ggggcgaacg 660
catctcgtcc ctgcgggtgg ggctacttcc acttgtcatc tttggcacca tgatggggct 720
gtttctcacg ggtgttacaa gcctcgttga aagctcagcc gttggtgctc tgctggcaac 780
tctcgcagcg ttgttcagca agcgtctgac gaaagttgtt tgggagacca cgacacgcaa 840
tacgctgacc atcacctgca tgttcctctg gatcattctg gcggcccttt gcttctcgtc 900
ggtctatgac ggtcttggcg cggtcaaagc aatcgagcgg cttttgcttg gtacttttga 960
tttgtcgcct tggacgattc tgatcctgat gcttttctct ttcatcatat tgggcatgtt 1020
cctcgatgac accgccatgc tggtcattgt ggcacctctg tatatcccgt tggtgaagag 1080
ccttggtttc aatcccatct ggtttggcat tctctatacg atcacttgtc agatcgcgta 1140
catcacgccg ccattcgggt acaatctctt catgatgcga gcgttggcac caaaggatgt 1200
gacgctgatg gatatttatc gatccatcgt gccattcttc ttcctcatgg tgctgaccat 1260
tatcattctg atgatctttc cacagatcrc gatgtggttg cctaactggt acatgggccg 1320
ataacaggat ctcgaaggga gaacgcataa gcatgaacgg tcaaaagagc cgctaatggc 1380
caagccgtta aaatagcagg gaacttcaaa cacttaatgg gagaatgggc atgagtgaga 1440
ataacaagct taacaaacgc gactttctca aaaaggccgg gctaaccact gtcggtgcca 1500
ttggcgccac gacacttgca acgccttatg tgcgggctca gagcccaatc aagtggcgtc 1560
ttcagaccta tgcgggtccg gcactcgcag aacacgtcat caagccgtct atcgatgcct 1620
tcaacaaggc agcaaatggc gaaa 1649
<210> 9
<211> 9915
<212> DNA
<213> Stealth W rus
<900> 9
gagctcgaac gttcgggaag atgtcatgag aaagccgcct tgctgtgatg aagaacttgg 60
tcaagtctcg gcgcacggcg ttgctccaac aatcatcaga atgcactccg atgggcacgg 120
aaatgcacga gattgtctac cggccgcctc ttgcgatgac ggtgcgcaaa gacatcgctg 180
tggtgatgtc attgacaccc ggtagagccg cgaccatggt ccagacgtct tggatgcgtt 290
cgggtgagag ggcttccact cggacaacca agtcaagttc gccagccacc acgtcgcact 300
gcacgacttc ggggatttgt tgaagtgctg cgagaacatc ggcgccgcgc atccggtcct 360
gtcgatagac _gagcatggtg gcactcaccg gcggcgctcc gacaggcctt tcctgaatgg 920
tgtagccgag gatgtgcccg tcccgctcta gacgctcgat tcgttgacga acggcatttc 48~)
gcgacagtcg tacgatctca ccgagctgcg cgtgacttgt gcgggcgttc tgtcgaagct 540
cgacgaggat cctctggtcg atggagtcaa gcggacgcat gcctaaaccc tccctggtgt 600
accgtcgggc ccgcaccgag ggccgtgcgg gcggcaactt gcacgtgctc tgccagcgct 660
CA 02282858 1999-08-24
WO 99/34019 PCT/US98n7744
tgcagcgcgc gggactccag agcagcaaac cgtaggtagt aacgttcggt cgctgtcgct 720
gtggacacgc gatggaggcg gcccatctga atttctcttc tcgcttcgta ccgcggaagt 780
aggccccacg cggcgccctc cagcagtagg gctttcgctg cagaggtcga tgccactgtg 890
gatagcgcac ggcccggcga gaaggatgcc gcttcagcga aggcgtgatg gcgagtctct 900
cgtccgcgaa cgatcacggt cggcgcagag gcgaaatctg catggtggac gcctcgcgca 960
atccactggt cgatgaaacc cggggtcgcc accgcgtcga acatccccac gccgagatcg 1020
acggtatgga atccggacat ctcctcagag gaagtggtga tccgaaaagt gatgtcatca 1080
ttcgcaggcg actgaccctt cagcggctca tcgatgatcg tcagatccat cggcgtgacc 1140
gcagcggcgc gcgcgaccgc ggaaagccac accgaaccca gatcgacctc cacagcgacg 1200
gtcgcgcggg ca-cgacaagc gccgtctgac agtagaccca gggtgcggag cgtctccctc 1260
tcgagcatct cggtctgacg agcaaaccga acgatggacg cccccgtgct cgtcagacgc 1320
actggctttg agcgcaccaa tacgacctga ccaagaagag tctccaaagc cttgagccgc 1380
tggctcacag cggagggagt aatgcggagt tcatgcgctg caccgtcgag agatcctgcg 1440
tcagcaacag cagcaagagt gcgggcgaga tcacccggaa gagtggtcat gagttaccac 1500
ctttcccggg tcgcgatgcg agcctgtcga gagcagcaac gcccgctgag gtcacagcga 1560
ccgccgatgc aaggagcact ggtagccagg catccacagc gatgagagtg cccgcggccg 1620
cagtccccag cgacccggcc gtgatcttca aggctccgac ccagacgaag acctgactgc 1680
gcgcagccac cggcgcatac tcgcttcgtg ccgcgagcgt tgcggcgaag aagtacgagt 1790
tcaggattcc ggtgagtgcg tacgccgcga tgacccagct gacgttgccg gagacgaaca 1800
caccaagcag gctcagyccg acgcctgccg cgagtaccgg cattgccttg tccgcatccc 1860
cacggagcgg ccggaccatc acgcccacgg aacccgtgaa gctcccgagg ccgtacgcgg 1920
tggtcaagaa gcctgccgct gcgggtgcaa ccccgaatcg ggtggcccag cgacggygac 1980
tgaccggcaa cacggygacc gacagggcaa ccgcaaccgt gccgtacaga gtgcgccgga 2040
gagggcccga actgagcatc acgcgccagg gtccgccatg gacgcggcac gtyggaaggg 2100
gtaacgtcct ycgacgaggg cggcagcacc ttcaccagaa atgcggtgaa ggcagcgaag 2160
ccggccagca caagaaccgc cccagtgggg tcccacgctg cagcgatgac cgccaccaca 2220
gtagggccga cagtacctcc gataccgtag gtggccacat cccatccttg agcgcggcgc 2280
tgcgtctctc gctcgggtcc ggcgatggcg ggcaggcgag aactgattcc accggtgagg 2340
agggggccga gtgcgccgga tgcgatcagg agaagggccg gaatgcctat ccagacgacg 2400
tcgtagagca cgacggcggc agccaacgtg gcggcatgaa gaacgcaggc caatgcaaga 2460
acgttccgcc catcgcgcgc agtgtccagt atccgcgcga tgaacggccc gatcaggtgg 2520
ggaaaggtga tgcacgcccc caagagaccg gcagcccacg ggggtccacc gacggtggtg 2580
acgaggagca cgacacccac caccgcgcca ccgtccgacg tgcgcgcgag agtcgccgcg 2690
acgacgtatc gtgcgagtcc tccccggcgc ccgtcggacg gctgattcac ggtgtgctca 2700
acactttcga tgccatggca gcagcgacga cggcttcacg ttcggtttca ctgagcccga 2760
caatcggaag cgggagggca ttgctctgcg tcagaccgat gtgctcggcg agcgcggcga 2820
cgactcggag gcttccgtac tgacggttcg ccgcccagag gggctggagc tgccgagaga 2880
tcagctcagc ttcctcatgg tctcctcgtt gcgatgctcg tgtgatcgcc aaggcaggct 2940
caggcaaggt accggcaatc accgagtacc acgcctcgca cccggcattc aggccagtgg 3000
ctgcgagcgc gtcaccggac actccaatgg ttacggcctc aggcactcgt gcacggatct 3060
ccgtgacgcg ccgagtcgcc tcggcaggac tctccggcac gcccggaatc ttgatggacg 3120
caacatgcgg aagtgtcgct actcgggcat ataggtcgtc tgtgaactcg aaatgcgttg 3180
ttcctggatt gtcgtacacg atgagaggca cgtcgaggtt tgcagtgacg gtgctgaaga 3240
gtccgaagac gtcctcctcc gtcagttgtt gatagctcat ggcaggcagg agcaggccag 3300
ccactccagc cgtctgagca tcctctgcga aggccaacac atctcgtgtg cgcagtgccc 3360
cgatgccggc gaagaccggc accgtgcccg ccagctcaag agcgatctgt atggcgctcg 3420
cgcgctcgcg ccggtccagg tacgcatacg atccggtaga gccgagcgca gtgatcgaat 3980
cgactcctga tgcagcgagg tggacgatga tccgagcgaa cgaaatctcg tccaggcctt 3590
6
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
catcccgaag cggtgtgagc gggaacgcgc wgagcccgct gaacaatgcg gtcactgtcc 3600
ggtccttcgc gcgccagtga tctccgtccg gtccagggcc garcgkatgt cagcgatgat 3660
gtcgtcggcg gactccagtc ccaccgacag gcgaaggtgc ccgtaggtaa ggaatccggc 3720
cggatagctt tcgcttcctc cgcgcgcgtc cggtccgacg tggacaatga gcgtttcatc 3780
atggccgagg gacaccgccg aggtgatcac accaaggttg tcgacgaagc gattctgcgt 3840
gtcgctgtcg ccgtcaacgg cgaaggcgag catcccaccg aatcctcgtc caccgaactg 3900
tcgcttggcg agttcatgct gtgcgtggga cgcaagaccc ggatactcca cgtaagcaat 3960
gcggggatca gattcgaggt actctgcgac gcgctgcgcg gaggcgaggt gctgcgcgag 9020
tcggagcgga agggtgaccg acccgcgcat gatcatccac gcgttgaacg gggagatcac 9080
ccctccaacg tcgacgacag cgacgtggcg gatgtgctcc accagatcgg agctgccgat 4140
gacagcacca cccatggcat caccgtggcc gttgatgtac ttcgtcagag agtggatgac 4200
caggtctgca ccatccgcca ggggacggta gaacggcggc ggcgtgaacg tgccgtcgac 4260
cgtgaggagc gctcctgctt ggtgtgcgat gtcggcgata ccgcgaatat ctgcgacctt 4320
cgtcgtcggg ttcgcgatgg tctcgacatg gacgagcttc gtgttggggc ggattgccgc 4380
acgcacagcg tcgaggtctc caacatccac gaaggtggcc tcaatgttgt accgctcggg 9940
gaggagttcg gagaacagct tccagacagc ttcgtatgtg acgttcgaaa cgacgacgtg 4500
atccccagtc ttgaggaggg tgaagaagac accgtggagg gcagcgactc cggttgcgaa 4560
agtggcggcg gcctcgccac cgtccatgac ggcgagcttc ctttccagcg cctgctggtt 9620
cgcaccgccg ttgcgcgtgt aggtgagccg gtcagtggca gaccagtcca tggacgcagg 4680
gtcatccgga aggcgatacg agttggccat gatgagcggc gtgcggacag ctccggtacc 4?90
ttcatcgatg gtgttgccgc cgtggaccgc ccaggtaagg aagtccacag tgtcggcgtt 4800
gtgcttgtcg ggtcgagcgg tcatgttggt cttcctccta gttcgttcct gcagcgagaa 4860
ttcgctgcgc gaccgtgatc tggtcgccga gtcggctcag ttcatcgacg agctc 9915
<210> 10
<211> 246
<212> DNA
<213> Stealth virus
<400> 10
gagctcgggg atgttgatga gtccggccac cgccgtgaag accatggcgg ccagcgtcgc 60
ctccggcagc aggctgagca caggagcgag gaagagcgcg accaggacgg ccagcgcgac 120
cgtcgtcagc gtcgccagct gggagcgggc gccggctccc tggttgaccg cgctctgcga 180
gaatccgcct gctgcgggca tggccgcgaa gaatgcgccg acggtgttcg ccgccccggt 290
cgcgaa 296
<210> 11
<211> 9192
<212> DNA
<213> Stealth virus
<400> il
gagctccatg acctttgagc aaatgctatg cgatcaggtc gagtagattg acaaaaaagc 60
agaggaattt ttcgcaaaac tgtcatttgg aagctgattt gggctagccc cccgcttgcc 120
ggatttgcac tgcgagacta tggtgcaacg ccttgcagct attctggcgc ggttaaaagc 180
cagtgtggta ttgtcaggtt ctgtctttat ttctcaggag ttcactgatg ctgaaaggct 24~7
cgattactgc acttgtcacg ccattcgata gtgaaggagc gttcgacgag aaagcttttc 300
gtgacttcgt gaactggcag attgaagaag gcactaaagg tcttgtaccc gttggcacaa 360
7
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
cgggcgaaac gccgaccttg tcccatgatg agcataagcg cgtcattgag gcctgcattg 920
aagtagcagc aggtcgcgtg ccggtgattg cgggtgcagg ttccaataat actgtcgaag 480
caatcgaact tgctcagcat gccgaaaaag cgggcgcaga tgcagttctt gtcgtcactc 540
cctattataa caagccgaac cagcgcggcc tctatgagca tttttcacgg gtcgcacgtt 600
cgatctcgat accgctcatt atctataaca ttccgggccg ctccgtcatt gatatgacac 660
cggaaaccat gggcacgctt gtgcgtgatc acaagaacat catcggtgtg aaagatgcga 720
caggcaagat tgagcgtgtt tccgaacagc gcggcacgtg tggcaaagac ttcatccagc 780
tgtccggcga agatgcgacc gctctcggct tcaatgcaca tggcggcgtc ggctgtattt 840
cagtgacgtc caatattgcg ccacgtcttt gcgcagagtt tcaggatgcc tgccaggctg 900
gtgactatgc caaggcactg gaactacagg atcgcctgat gccattgcac aaggcgctct 960
tcatcgagcc caatccttcg ggtccgaaat atgctctgtc gcgccttggt cgcgttgaaa 1020
atgttcttcg ctcgccaatg gttgtaatcg aagcagcaac cgctgagaag atcgatcagg 1080
ccatgaagca cgccggtctc acgaattaga gtatttccag ccaaagtgcg aagcggtttt 1140
gcgttggatg ttggataatg tgtttaaacg agctttcaga gcgtgtttct atgcgatcca 1200
tcagcagaaa atacgctcta aggctgctaa ttttgcccgg ttgagtgatt tttacgctct 1260
tgctcatgcg agagcgtttt catttccggc aatgagcatt atatggtgcc attatgaata 1320
agccgaaaaa ctctcccgcc cgcaaaatgg tcgctgaaaa ccgtaaagcg cgctacaatt 1380
tcgagatttc tgatacgctc gaagctggtc tggttctgac cggcaccgag gttaagtcct 1490
tgcgcgccaa tcaggccaac attgctgaaa gctatgcaag ctttgaaaac ggtgagttct 1500
ggctgatcaa ttcctatatt ccggagtata cgcagggcaa tcgctttaat cacagccgcg 1560
ccgtttacgt aagctgttga ttagccgtcg cgaaatggca cggattttca attcggtttc 1620
acgcgaaggc atgaccgtcg ttccgttgaa gttatacttc aacgatcgtg gtagagctaa 1680
gctggaaatc ggcgtggcgc gcggtaagaa gaatcacgac aaacgtgaga ctgagaagca 1740
gcgcgactgg aatcgcgaga aatcacgtct tctgcgcgat cgtggctgaa gcgaaaatac 1800
tgttcaaaga aaaagagcgc tgaaaggcgc tctttttata aatgatgcaa aagggttcat 1860
gaagttcgaa attatgaagc tgcacgaacc tgacgattgc gcatatcagt agtcttcgtc 1920
aagatcttcg tcctgacgac gctgctgttg ctgtgggcgt tccgaaggat cgcgtccaat 1980
ttcagctttc agcgaaacca gatcgataaa atgatcggcc tgacggcgca attcatcgga 2040
tatcatcgca ggctgtgtcg tcagagtgga aacgacggat accttacgac ccttgcgctg 2100
caatgcttcg gcaagcgaac ggaaatcgcc atcgccagag aagattacga aatgatcgac 2160
ggtgtcggtg agctgcatgg catcgacggt aagttcgata tccatgttgc cttttacctt 2220
gcggcggcct gtcgagtcgg taaattcctt ggctgccttc gtgacaacct tatagccgtt 2280
gtaatcgagc caatcgatga gtggacggat cgatgaatat tcctgatcct caaccagagc 2340
cgtataataa taggcgcgca gcaaatagcc gcgtttctgg aatgccttca aaagtttacg 2400
gtaatcaata tcgaaaccga gtgtttttga agctgcgtat aaattggcgc cgtcaataaa 2460
tagcgcaatt ttttcacgag aatcgaacat cgtgcaatat atccactctg cggccggtag 2520
gragtgggcc tgcgaccgcg tattcagatt tgtttcttaa acggcggggg tattcatttt 2580
taccaatgac gtttattgcg ttctacggag atattataga aaahcaagca accgatggtt 2640
gttatttgat caatcttaat tacttttacg cgatatttcg atatagcaat cgataatcga 2700
tcaaaatcta ttgttccaat ttgatccaga tcgtgtattt gtcagacaga ttaatgaaca 2760
gttgtatctt agcctagatt tctgagcctt gtcgttggtg ttttgcgctt ttgcttgtaa 280
tttcggctca caagcgttat gtgcaagaaa aattccgtta aagtttaaga aatgaaaggg 2880
accgcctatg gcccgcgtca ccgttgagga ctgcgtagat aaggtcgaga accgttttga 2940
actggttctg ctggccggtc accgtgcccg ccagatttct cagggcgccc agatcacgat 3000
cgaccgcgac aacgacaaga acccagttgt cgcgctgcgt gaaatcgctg acgagacact 3060
ttcaccggat gatctgaagg aagacctgat ccattcgctg cagaagcacg ttgaagttga 3120
cgaaccggaa gctgctgctc ctgcccagat caccgatgct tccgatgcgt tggctgaagg 3180
gattgccgaa gctggtgaag acgatgtcgt ttccttcgac cgtatgtcgg aagaagaact 3240
8
CA 02282858 1999-08-24
WO 99/34019 PCTNS98/27744
gcttgctggt attgaaggcc tcgttgctcc agaaaagaac gacgacttct aatcgtcgct 3300
ctgctgatca agtatttcag gcaaacgtcg aaatgagttt tgcctcattg~aatacttgaa 3360
tacaaacagg ccttggtttt ttgcgtgcgc ttcggcttcc aggctgtggc gcacgttttt 3420
atgtgcatgg caggctggga attgagatta gcttttggct tgccactgag acgtttgtga 3980
ctgaaattaa gcctgttggc agaaaacagg tccggaaact cgcaaattgt tatatttttt 3540
agtgatttcc gttcaaaatg accgctgcgt acgtgactgg tagggagttt ctgtaaatga 3600
tgcgccaata tgagcttgta gagcgtgttc agcgatacaa gcctgacgtc aatgaggcgc 3660
ttctcaacaa ggcgtatgtt tacgctatgc agaagcatgg cagccagaag cgtgcgtccg 3720
gtgatccata tttttcccac ccgctcgaag ttgcagcaat tctcacagat atgcatttgg 3780
atgaggcaac gattgcgatt gctctcctgc atgacacgat tgaagacacc acagctaccc 3890
gtcaggaaat cgatcagctg tttggcccgg agattggtaa gctcgttgaa ggtctgacca 3900
aactcaagaa gctcgatctg gtttccaaga aggcagtgca ggcggaaaac ttgcgcaagc 3960
tgctgttggc tatttccgaa gacgtgcgcg tgcttctggt gaagcttgca gatcgactgc 4020
acaatatgcg tactcttggc gtgatgcgcg aagacaagcg tctgcgcatt gctgaagaaa 4080
ccatggatat ctatgcgcca ctcgctggcc gcatgggtat gcaggacacg cgtgaagagc 4140
tc 9142
<210> 12
<211> 198
<212> DNA
<213> Stealth virus
<400> 12
gagctcgtgg atgcgctgtt cgcgaaggcc gacgcggtcg tgcactatgc ggcggagtct 60
cacaacgaca actccctgca cgaccctcgg ccgttcctcg acacgaatat catcggcacc 120
tacacgctgc tcgaggcggc acgtcgacac gaacgacgtt tccaccacat ctcgaccgac 180
gaggtctacg gcgacctc 198
<210> 13
<211> 4626
<212> DNA
<213> Stealth virus
<400> 13
gagctcttca cgaaaatcat caacatcgtc gcgctcgatg gcatcgagga cctcatagac 60
ttcctcgagt gtataaggcg cgattgatct ggaggtctgt tctacgtccc agggacagcc 120
cgtttcgggg tcacgaaggg caaccatgat ttcgagaaga cggttgatat tgcgggaggg 180
ttccatcttc gctccattaa aattgatgtc gcattcttga ggcagtctgc aagaatcgga 290
gggtttgggt tgcagttcgc tacggttttt gcatagtcag ccaacaaacg ctctcgggat 300
cgcacattgg ggctgtatgt tcaacaagca ggtatttaaa gcatgacgat tcttgtaact 360
ggtggcgccg gatatatcgg ttctcataca tgtgtacagc tgatcgaggc cggccatgat 420
gtggtggtgg tcgataattt cgataacagt aatccggaag ctctccatcg cgtggaaaaa 480
atcactggtc gcgcacctat tcgcgaaccg ggcgatattc gcgaccgtac tttgctggaa 540
cagatcatca cgcgtcataa atgcacggct gtcatccatt ttgccggttt gaaagcagtg 600
ggtgagtcga gtgaaaagcc gttgcattat tatgattgta atgtgcttgg cacgctgcgt 660
ttgttgcagg ctatggaagc cacaggcgtc aagacacttg tcttcagctc gtctgcgacg 720
gtttatggcg atccagaaaa attgccgatt accgaagatc agccgctttc cgcgaccaat 780
ccatatgggc gcacgaagct tattatcgaa gatatgctgc gcgatcttta taacagcgat 890
9
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
aacagctgga agatcgcgat cctgcgttat ttcaatccgg tcggcgcgca tgaaagcggc 900
ctgatcggcg aagatcccaa gggtattcca aacaatctga tgccgatcat cgcacaagtg 960
gcaaccggcc gccgcgaaaa gctcaacatc tggggtaatg attataatac gccggatggc 1020
acgggggttc gtgactatat ccatgtcgtt gatcttgccg ccggacatct caaggcgctc 1080
aagaaacttg atgaaccaaa gtgcttttct gtcaatctgg ggacagggca gggctacagc 1140
gttcttgatg tagtaaaagc cttcgaacac gtttcaaatc gtgaaattaa atatgagctt 1200
tcgccacgcc gtctgggcga tgtggccgag tgttatgccg accctgcttt tgcacgtgat 1260
ttccttggct ggactgccga gaaaaatctt caggaaatgt gcaaggacat ctggaactgg 1320
cagtcgaaaa atccaaatgg atatgagatg gattgagggt tgaaaggccc ttatgcagct 1380
cattttcccg gaaaagtgat ccgattggcg gctaactccg tcctttagtg ttgtgccgat 1440
ttctgatcgg cttattacaa actagtggat tgaatttgac ggttgaatcc cgactgacat 1500
acatgctgtt tcaaacgtca aattcgaaaa atccactaga ttcataaact tgctagtggt 1560
catcttgatt ccgacatttg tccgacgcca gtatccgagg gatgcaaata tcggaatcag 1620
accgctaggg atcacaacta gctcggaacg ttctcggagg catgtgtgtg tgttcttggg 1680
tagcgttcaa gtatgaagtg ctgaaggact gacgagaaat gcgttttctg cccgataagt 1740
tcacctgcat gttgattgcg accattctgc ttgcatcatt tcttcctgtg cagggtgatt 1800
ttgctgaatg gttcggaatt gcaacaaaga tcgcagtcgg tcttttgttc ttcctgcacg 1860
gcgcgcgttt gtcgcgtgag gcagttgtgg ctggcgtcac tcactggcga ctgcatctgg 1920
cggtcgtctg ctcaacattc gtcctgtttc caattttggg actgaccgca ggctggacta 1980
ttccggggct tgcgcaatcg ccgttttatc tcggtatcct ttatctctgc gttcttcctt 2040
caaccgtaca atcttcaatc gcctttacct ctatggctgg cggcaatgtt tctgcggcca 2100
tcgtttctgc atcggcatcg aatattttcg gcatgttcct gacgccgttg cttgtcggac 2160
tgctgtttgc ggttaaaggc ggcggcggga tttcagtcga tgcgctggaa gcgattttgc 2220
tgcaattgct tgcaccattt gttctggggc aaatcttgca gccatggatt ggtaatttca 2280
tgcgtcgtca cagcaaatcg cttggctttg tcgaccgtgg ttcgatcctg atggttgtct 2340
atctcgcatt cagcgaggct atcgttgaag gcctgtggca caccgtttcc tggaacgatc 2400
tttgcgtcat gatcggtgta aatatcctgc ttctggtgat cgtcatgctg gccacatggt 2960
atggaagcaa gtggttcggc tttaatcacg ctgaccgcat caccattatg ttttgcggtt 2520
cgaagaaaag cctcgccagc ggcgcgccga tggccagtgc gatctttgcg ggcgcgaatg 2580
tcggtagtgt cgtgctgccg ctcatgctgt ttcaccaaat tcagctgatg gcttgcgcag 2690
tgattgcgcg caaacttgcc gatcataagc ctgcttccag tacggcaact gcggcggctg 2700
aatagaactg gttcttgctg tcatcttcat atgagggtag gagggcaggc gagtagttcg 2760
cctcgccctt tccatctatg gaacaggcgc cgtaacccgt ataatagctc tctactggcc 2820
ttttcagttc gctgacggct caacaaaagg caacgcagat gtccaagcag aacggcaaat 2880
cccataacat ggattctctt gaccaagagg cgcttgctga ggcttacaac catgcgcttg 2990
ccttggaaaa ggctggcgat ctggatgctg ctgctgaggc ctataaagca gttctcgaaa 3000
ttgatcccga agaccacggt ggcgctgccg tacgtctcgc aagcatgggt cgaggaactg 3060
tgccgccgaa agcaccggac gcttatgttg caacgctgtt tgatcagcat gccgagatgt 3120
tcgatacaat tctcgttgat cagcttggtt acgacgtgcc actgcaattg cgtgaaatgc 3180
ttctggaact ggatgaagag tttcaggccg agcgcatgct ggatcttggc tgcggtacag 3290
ggctttctgc cgatgcgctg gacgacatgg ccgatcacaa gaccggcgtc gacatatctg 3300
aaaacatgat cgaagtggct tatgaaaaag gcgattacga tgcgcttttt gtcggcgaag 3360
cagttcgttt tcttgagacc acagaggaag acgcttggga cctgatcgtc gcaacagacg 3920
tgttgcctta tatgggcgag cttgccgctt tttctcgggc gttgcggagc atctgcggac 3980
tggaggctat ttcgggttct ccagtgaaac gcagtcagat gagcgtttcg ctggccgtga 3540
tttcatggtt ggcgattttc aacgttttgc acatgcgcag tcctatgtac gttcgctgct 3600
ctcagaacac ggtatggact gtattcgttg cacggatatc actgttcgaa gtgagcaagg 3660
atcgccagtt ccaggacatc tctacatagc tcagcgccgc taacgtttat tgggtcttgt 3720
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
gtgcgaactt agatcatctt gttccataat ctatcttatg tgattacgac atgtaggggc 3780
tatttagtaa tgcgacagtt gggccagtta gagatgcgac gtgtcgcctc ttgaggtgct 3890
ggtcaatgtc aacgttggag gcaaggatga cgatcttcag tctggttgag accatgagcg 3900
gttggagtcg tcatgccctg tttgatcacc atgtcgcaga aagaattgca tcgcctcgaa 3960
gtcgtccaga agatccgtga tctacgcctg agcgttgtcc aggcggctga gctgcttggc 4020
ctcagtcgaa gtcaggttca caggctgctg caagcctatg accgggatgg tccagctggc 9080
ctcgtttcca agaagcgatc gcgtccgagc aaccggcgtc acagcgagga tttccgtaat 9190
acggcgctgg acctgatccg cgaacgctat ctggatttcg gtccgacgct ggcgcgcgag 4200
aagctgatcg aactgcaccg gatctctgtt gccaaggaga cgctgcggca atggatgacc 4260
gaggccggca tctggatctc gcgccgggag cgcaagaaac gggttttcca gccacgcggc 9320
cggcgcgact gctttggcga actggtgcag atcgacggct cgcatcactg gtggttcgag 4380
aaccgcggcc ccaaatgcgc cctgctcgtc tacatcgatg acgccaccgg caagctcttg 9440
catcttcgct ttgccggatc ggaaaatacg ttcgactatc tgcatgcgac gaaggcttat 4500
ctgcagcaat ggggcaagcc gctggctttc tacagcgaca agcacggcgt tttccgctcg 9560
ctccatgcgt cgaagaaaga ccggacgagc ggtctgacgc agttcggccg ggcgctttac 4620
gagctc 4626
<210> 14
<211> 9199
<212> DNA
<213> Stealth W rus
<400> 14
gbbbcgaatt ctggtatgag acggacggca cgccgttcaa tcccggaaat tattacaatg 60
tcggcggcaa ttccaaattc tatggcgcag tgctggtgcg ctatcggcgc gaagattttg 120
aggagcttgc gcatcttgaa ggcgtgtctc cggcatggcc ttttggctat gatgaacttg 180
agccctggta ttgcaaggcg gaagcgcttt ttcaggtgcg cggcgagctt ggcgatgacc 240
caaccgagcc gtatcattca aagccttatt cttatcctgc aatcaatgat gaacatccga 300
ttgccgatgt acgtgagcgg ttgaaaaagg cagggctgca tccggcttcc ttgccactgg 360
gtgttgatat cgagcgctgg ctggcaaagg ccaaaacgcc gtgggatgcg catcccaaca 420
gcaatgacgg caagatggat gcggaaacct gtccgttagc actcgcactc aaacatccaa 480
atgtccggct tgaaacatcc gcgcgggtaa cgaagctgga agccgggccc gacggaaaga 540
ccatcacggc agttcattat gtgaagaacg gcgaggcgct ggtcctgcgt cccaaactgg 600
tcattctatc tgccggtgcc gtgcaatcgg cggcacttct gctgcgttca ggactggcga 660
acggttcgga tcaggtcggt cgcaatttca tgaaccacaa tgccagtgcg gtgatcgggt 720
ttgatccgcg ctatcgcaat gacagcgttt accaaaaaac gtttggcttc aatgattatt ?80
atctctcgga tggggctggc gggccgcccc ttggcaatgt gcaattgctg gggagggttt 840
caggcgcgat cctgaaatcg aatatgcagc gagtgccgga atggcttttg aaccgcattg 900
ccggacacac cattgatttt tacgcgatga gtgaggacct gccatcgcca gaaagccgcg 960
tgagcgtgga tggtgatcgc atcattctgc attgggtgcg ttccaactgg aaagcacatc 1020
tgatgctggt tgataagctc aaatccgcgc tcaggcaggc gggctttcca attgtgctgt 1080
cgcgggcctt tgaccggcgt acaccatcgc atcagtgcgg cacggtgcgt attggcaatg 1190
attgcgcgac ggcgccactt gatccctggt gccgtgctta tgaccaccct aatttctatg 1200
tggtcgatgc gtcgtttctg ccgacctcgg ctgcggttaa tccggcgcta accattgcgg 1260
cgcaggctct gcgcgtatcc gaccacattc aaagcgaggt gctggcatga accgtcaaag 130
acctgtggca ctggtaaccg gcggctgtcg cggcatcggg cttgggatag cgcgtgcgct 1380
tgccgccaag ggttttgatc tcgccattac cgatcgcgaa agcgacgacg ctgtcattcg 1440
tgaactacgg gaacttggcg gaaaagtggc tttctttgaa agcgatcttg ccgcggttga 1500
11
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
tacacatgag gcggctgtat cagctgtcgt gagcgaactc ggtggcattg attgtctggt 1560
caacaatgca ggcatgggct caattgagcg aggcgatttc cttgggctga agcccgaaaa 1620
cttcgacacg atcatggatg tgaatctgcg cggtacggtg tttttcaccc aggccgtggt 1680
gaaggccatg gtggcggtga acgaggtgcg ttttccacgc agcattataa caatcagctc 1740
cgtttcgtcg gtgatgacct cgcccgagcg gcttgattac tgcatcagca aagcagggct 1800
gacggcattc acgcaaggac tggcattgcg tttggctgaa gcgaggatcg gcgtgttcga 1860
ggtccgtccc ggcatcatcc gcaccgatat gacggcgaaa gttgctgagc gttatgacgg 1920
actgattgaa gccggtctgg tgccgatgaa gcgctgggga gaggcgggcg atgtcggcgc 1980
gattgtggcc ggacttgccg gtggcgattt catttttgcg acgggctcgg cgatcaatgc 2040
cgatggcggc ctgtcgattg caaaattata agggtaaggc gatggattac gattatatca 2100
tcgtgggtgg tgggcctgcc ggctgcgttc tcgccaatcg tctgagcgaa gatgcttcgg 2160
taaaagtgct gttgctggaa gctggtggta gcgactggaa tccgctgttt cacatgccag 2220
ccgggtttgc caagatgacc aagggtgtgg cgagctgggg ctgggaaacc gttccgcaga 2280
aaca.cctcaa aaatcgggtg ttgcgctata cgcaggcaaa agtcatcggc ggcggctcca 2340
gcatcaatgc gcagatttat acgcgcggga atgcagccga ttatgatctt tgggccggcg 2900
aagacggctg taccggctgg gactaccgcc atgtgctgcc ctattttaaa cgcgccgaag 2460
acaatcagcg tttcaacgat gatttccatt cctatggcgg gccgcttggt gtttcgatgc 2520
catctgcgcc actgccgatc tgcgacgcct atatccgagc gggccaggaa ctcggcattc 2580
cgtttaatgc ggatttcaac ggtcgcgaac aggcaggcgt cggcttttat cagctcaccc 2640
aacgcaaccg ccgccgctcg tctgcatcgc ttgcttatct gtccacgatc aagggtcgca 2700
agaacctgac gatccgcatg aatgcaccgg tgcgcagtat cgaaatggag aagacgcgcg 2760
tcaacggcgt aacgctgatg agcggggaga ctttgcgcgc aagccgcgag gtgattgtat 2820
cgtccggcgc gattggttcg ccgaaacttc tgcttcaatc cggcatcggc tccgcggatc 2880
atctgaaaaa ggtcggtgtc gcggtcaagc atgatctgcc gggtgtgggc gagaacatgc 2940
aggaccatct cgacctgttt gttattgccg aatgcacagg cgatcacacc tatgatggcg 3000
tggcaaagtt gcatcggacg ctgggcgcgg gcctgcaata tatctttctg cgctctggtc 3060
cggtggcgtc cagcctcttt gaaaccggcg gcttctggta tgctgatccg gatgcccgct 3120
caccggatac ccagtttcat ctggggcttg gttcgggcat cgaggcaggt gttgagaagc 3180
tcaaaaatgc cggtgtaacg ctcaactccg cctatctgca tccgcgttcg cgtggaaccg 3240
tgcggctggc atccagcgat ccggcagctg cacctctgat cgatcctaat tactggagcg 3300
atccgcatga tcgcaagatg tcgcttgaag gtctgaagat cgcgcgcgaa atcatgagcc 3360
aggatgcatt gaaaccttac gtgatggccg agcgtctgcc ggggccaaag gtcgtcagtg 3420
acgatgatct gttcgattat gcttgcgcca atgccaagac cgatcaccat ccggtcggca 3980
cctgcaggat ggggacggat gcgatggctg ttgtcgatct tgatttgaaa gtgcgcggtc 3540
ttgaaggtct gcgggtttgc gacagctcga tcatgccgcg cgttccgtcg tgcaacacca 3600
atgcgccgac catcatggtc ggcgaaaagg gggcggatat tattcgcggc ttcgatccgc 3660
tgccgccggt cgtgttttca tgggagaaaa acgagcagaa gcggcgtgca aggatttagt 3720
cagccttggt ttcatcaaat ggttcgaaac gcagatagcc agcaatgccg gaacctttgt 3780
agttgggatt gtcggatggg tggttcacgc cgtcattgac gggaataacc ttgaagtcga 3840
agggagaaac gccttcgagg caggccgcat tcacgccgaa ctggtgcggg ctggagcggc 3900
gctggtggaa ggtgtaaatc ccgcatttcg agcagaagaa gtgcttcgcg gcacccgtat 3960
taaacgtgta gagcgtcagc gcatcttcgc cttcaagaat ttccagtcca tccagatcgg 4020
cggagacggc aactgcaccg cgcatccggc aataagagca ggtgcaacgg cgcgccgtgt 4080
taaggccatc ggaaagtttg acgcgaaagc gcactgttcc gcagtggcag gcaccgttgg 4140
ctactttgat atcggggttc atgctggtct cctctttcag gaaactgata tttccatttt 4200
cacagcttta ccattgcctg aagttgatta aattgccttt cgagatcctt tgggagggaa 4260
ttttatgagt gggtttgcga ttgtcaccgg tggaagcacc ggcattggac ggcatcttgt 4320
ttccgcattt gcggaagccg gatatgcggt tgctttcagc ttcagaggcg atgacgaggc 4380
12
CA 02282858 1999-08-24
WO 99/34019 PCTIUS98/27?44
tgcaaataca cttatggaag aagtcgaagc tgcgggcgga caggcgttgg ggatcgaatg 4440
cgatgtcggt tctggagttg aggtcgaaga gttcttcgat gaagtctgca gctggtatgg 9500
tgatgcaccg gacgtactcg tcaacaatgc cggtatccag acttgggcgc cgttgctgga 4560
gctttccgag gaaggctggg acgatgtgat ccgcaccaat atgaaaggct gctttctgaa 4620
cacgaaagcc gctgccaaga ggatggttga cgtcggtaaa ggcggagcaa ttatcaatat 4680
cggttcgggc tgtaacaagc tcgcattccc gaagctcgtt tcctacacgg cgtccaaggg 4790
cgggattgag cagtttacca aagtgtctgc cgtggaactt gggccgcatg gtattcgcgt 4800
caattgcgtg gctcccggtg cgatttacaa tgagcgtacc gcccaggaac agcctgacta 4860
tgcagcaaca tggggccgga tcacgccact gcgacgggtt ggaaccgtgg aagacctttc 4920
cggtccggtg ctgtttctgg cgtctgatgc tgcgcttttt gtttcgggcc agactatctg 4980
ggtcgatggc ggcctgtttt cacaagccaa ctggccttat ggggcgtgag gaaaattaga 5040
tcggttccca cttttcggaa tgcgctttat cgtccgcgca tttgtgcgcc cgcgtctttc 5100
gagaagcgaa ggttccagaa ggtggccgtc agcgatatgc cggtcacaat aaagaaagcc 5160
atagagaaat ccgatgtcag cggtacgtcg cgctcatgcc aggccatgga cgtgtgaagc 5220
gcgagggcgc cgatacaaac gccgaaagaa agcatgagtt gctggaaggt tgaatagaag 5280
ctgttggccg agctcatctg cttttcatca accttgtcat aggcaaccgt attataggct 5340
gtgaactgaa acgacatcga aaagccggac atgaacagca cggcaaagat cagccaatgc 5900
ggccattcag ggctgaacaa accgcagatt gcgtaactgc atgacgagaa tatgccgttt 5460
acaaccagtg acgagcggaa gccgaaccgg cgaatgattt taggcgcaaa ggctttcatg 5520
gccatggaac caagtgcggt cgccaaaacc atattgcctg cggatacagc cgaaatgccg 5580
aaggctacct gcagcatcaa aggcaacagg aatgggtgcg cgccttgtgt gatgcgggtg 5640
atagaaccag cgaccatcga ggtgccgaag ctttcaatcc gcatcagtga aaaatcgagt 5700
agcggagccg ggtggcggcg cgagtgaatg acggtcgcaa tcgcaaacac aatgccaacc 5760
acaaagaact tggccgccaa agcgctggtg gtactggcac tttcaagtcc gaaaagcagc 5820
gcaccaagcg ctatgcccga caggatcaaa ccgataaagt caaaaggttc tttggtgtcg 5880
cttttatatt ctccgatata gaatgacaca aagatcatgc ccagaatgcc aatcggcaca 5990
ttgatgtaga agatccagcg ccagtcgagc caggtcacga acaggccccc aatgggcggt 6000
ccgaggattg ggcccataag cgcaggcacc agcatccacg acattgctga gatgaggtcc 6060
ttgcgctcga cagaacggat tagcaccaaa cgtccgactg gcagcatcat ggcgccgcca 6120
ccgccttgca acaggcgggc aaagaccaga aagggaaggt tcggcgcctg tgcgcagagg 6180
atagagccag cgatgaaaat acttatcgcg aagcggaaca cggttcgggt tccgaagcga 6240
tcagcgatct ttccgcttgc cggaatgaaa atggcgaggc tcagaagata tgatgtgagc 6300
gcgacactca tcgagggtgc ggcgacatcg aaatctttgg ccatggtcgg caaagcagtt 6360
gccaggatcg tagcatcgag ctgttccatc agcatagcac tcgcgacgat gagggcgatg 6420
atccggaaat tgcttttcgc ttccagtgac gcgttttgtt cactggtcga cgtttcagtt 6980
tcctggatga tagtcatggc tgcttcagct ttgcaaacgc gccgacctgt ctttcaaaac 6590
ggccagccta aagggtcgat catctgtgac gatctttttg gaatcaatct tcggtctggg 6600
gaatgtgtca ggaacggtta caaactcact cagaggatac gcgcccagtt gttggccaaa 6660
acgtcggaga gatgagaaag ctcgccacaa gaccgcgagc gggtatagca caaatggctg 670
gaaatcacag gacttcaaga taatttgagc gagatgggat cggccgttgc tgaggggtga 6780
atggtgatcc cgactggatt cgaaccagtg gcctcaagat taggaatctt gcgctctatc 6840
ctactgagct acgggaccag tcatcaaaaa cgcccggata taccggagca ttttccgaca 6900
catactgttt ttcatggctt tcgccaaccc cgcaaaaagc ggggcaggcg catttctttg 6960
catatcgaaa agcgtcaggc agcgagagcg gtttcaacca ctgacacgaa atagctaacg 7020
ccatatggaa tggcttcgtc gttgaaatca taggcagggt gatgcaggcc cggtgtgtcg 7080
ccattgccaa ggaagatata tgcgccggga cgcgcttcca gcatgtagga gaagtcttcc 7140
gcagccatca ttggagccac atcagttttc accttgcctt cgcctgccac attctttgca 7200
acgcgggcag caaagtcggt ctggtcgtca tgattatacg tgactggata gttgttcttg 7260
13
CA 02282858 1999-08-24
WO 99/34019 PCT/US98127744
tagcgcacgg tgatttccgc gccgctaacg gttgcgatgc ccgccgccgc ctcgcggatg 7320
cgacgttcgg cataggcgcg cgtttccttg ctcagtgtac gcacggtgcc tgagagtttc 7380
gccgtttccg ggatgacgtt ataggcttcg cccgcatgaa acttggtgat ggaaatgacg 7490
agtgaatcca gtggatcgat attgcgtgcg acaatgccct gaatggcaac atgcagctgc 7500
gaaccggcta ggattggatc aatcgtgcgg tgaggctgtg cggcatgacc gccgcgtccc 7560
ttgataagca ggtcgaactc gtcggttgcg gccatgatcg ggcccttgca catggcgaac 7620
tggccgaccg caaggctcgg caaattgtga acgccataga cttccgcaat gccaaagcgg 7680
tccatcacgc catcctgaac catggcgaga gcgcctgcgc cgccttcttc cgctggttgg 7740
aaaagcaaca cggctgaacc gcgaaaatta cgggtttcag ctaagtattg tgcagcacca 7800
agcagcatgg atgtgtggcc atcatgaccg caggagtgcg ctttgccagg attcttggag 7860
gcccattcga caccgctggt ctcggtgatc ggcagggcat ccatatcggc gcgtaggccg 7920
atggccggac catcgccatg gcgtcccttg atgaccgcaa cgacgcctga gcgcccaacc 7980
ccggtttcaa caagatcgca accgaatgat ttcaactttt cttcgacaaa gcgtgccgtt 8040
tcatgaacat cataaagaag ttcgggattc tgatgcagat gacgacgcca tgtggcgatc 8100
tccgcttgag tttcgacggc acgattgagc actggcattt cggaaatatc ctgcagattc 8160
tctttattca gaagaaacga gaatatgacg tttcggtgaa agcgggcaat ccctatttgc 8220
cttttccttg ccacatggca tagataagag cagtacaaat tctccttttt gactggtgta 8280
ttcgcaagcc gttacggctt ttcaaggtcg atacaacagg aagcggaacc gataacccgc 8340
aggaattgcg gctcttgttg attggaacta cgaaatgatt tcgaagtcgt tgaaaatctg 8400
gtttgcaact gcggcgattt ctagcctggc cttagctggt gctttatctc ctgctttggc 8460
aaatccatcg attgcggtgg atgttgcaag tggcaaggtc tactccgcgc aggatccttt 8520
ccagcgctgg tatccggctt cgctgaccaa gatgatgacg gcttatgtca ccttccgcgc 8580
gattgaagca gggcagctga cgctggaatc tcctgtgcgc atgacggtca acgcctcgaa 8690
aagagccacc gagcaagatg ggttatcgtc ccggmtcggt gatgacgctc gatactgcgc 8700
tcaagatcat gctggtgaaa tctgccaatg acgtggccgt trcggtcgcg gaagctgttg 8760
gcggtacgga atctgctttt gtgcagcgca tgaatgcgga agcacagcgc atcggcatga 8820
gtggttcgca ttttgccaat ccaaacggtc tgcatgatcc gaacaattat tcgacagcgc 8880
acgaccttgc cgtgcttggc gtgcagttgc gccgcgaatt ct*wgnnscs cvvyrkbr** 8940
*kbnnnrmam hadataragr ahntwhnmar tndatnstat hbcdcmgtms nwrmansymb 9000
arahbcwhnm artnwhnmar tnhddtbcbw hnmartnnrm awhnmartnm crstwrdrdh 9060
ccdbbcttdg danbbddaa* rtntrywsta bwrddcmnts mmarynrmat ndcmntsmma 9120
rynrmatnda thhdcmbtat hbcdcddmws tathbcdcda tnstathbcd cmcrstwrdd 9180
cmntmswrdd cwrddcmnt 9199
<210> 15
<211> 9181
<212> DNA
<213> Stealth virus
<400> 15
gbbhnbbcga attcattcat cttcatgggg cagcagaaaa atgaacatca ggaccagctt 60
ccacattgac accatggctg tcaccatgct ctttttcaac gggctgttca accttaacat 120
ctttcgagac gtagtggccg atgactcaca acaaaaaagt tgtgattata tgaaacaaca 180
acactttttt cgcacgatgg gtatagcctc tgtgtttctc agacccgtct ttagtcctat 290
catttacata tgtgtcagtc gtaaaatcat acagggtatc tgcaaattgt ttataaaagt 300
accaaaccat accataagct cggaacgtgt aaagcttatg tctccaaata gaatgaacga 360
cgatgcccca gagcttccgc ccagggaata tgaatccgcg ttctaaatta ttgcgcgttg 420
atagcgcaac gacacaacca gccgatatat gtttgagacc ggtcacaaac cccgacattg 480
14
CA 02282858 1999-08-24
WO 99/34019 PCTNS98/Z7744
caaatcgaca ttgttcgatt tgcgaacaga ctttttacaa acatgaacaa ctcctcctgt 590
aaccttctgc aagtgtttaa gatcgacgac gcatctcgcg atgtcagcgt cggtttctat 600
agcatcgcca tatgcgtcgg actcatagca aacatactga tattactggk cctaatcaaa 660
aggcgaaaac ttacctttgc cagcgacgtc tactttctga atgctaccat aggcgacatc 720
gttactactg scacgctacc cgatatggat gtattatgag ctcaactaca gccaattcaa 780
tcgagaagca tgtatcagtt tctccatcag cttctacacc cccctgttcg ttcaagcctg 840
gctcatgatc tccatcgcca tggaacgata ctccaatctg atatggatgg cacccattaa 900
aagaaaagta gccgtacaga attcaatcgt cgaggaccag tctgaactgt gatcgacccg 960
cgcgccaagc ttgccgctaa aggcggttgt gtaagcttcg ttggccgacg gcgcttttgc 1020
atcatattga ttgcgtcctc ggctcagaag accatcggca taaatcttgc cccagtcaaa 1080
atccttcgac agcgcgaagt tgaacgatcc ctgcaggaaa ccatcgcgat caggctcata 1140
accaaaagct tcgggagtcg tgaaattata gccctgcgtg ccggtcactg ccgcaccaaa 1200
ggcataatcg ataccatctt tgctgcgccc ttgcagagag ccggatacat aaccgcccca 1260
tgggtgcgtt acacctgttg tcacgcttcc gcagaaagag cgctcgccac acgctccgcc 1320
ctgcttggtg ataatgttga tgacgccgcc catcgcatcg gcaccgtatt gcgaggaatg 1380
cgcgcctttg gcgatctcga tacgatcaat tgagctcaac ggaatattgg aaagcgcagt 1440
cgccccggtg gtcgccgaag ctgttcgcac gccattcacc agaacgactg tctgtttcga 1500
tgacatgccc cgaatataga gattggaaga cgatccctgt ccgccatttg cggtgatcga 1560
aatgcccgga taatattgca gcagcgattg gagatccggt gaagcagagc gctcaatctc 1620
ggccttatca atcaccgtga cggaagacgt tgaacgctgc aacgatgtcg cgcggcgcag 1680
cggcgttaca acaatcatgt caagcacgac gccatcctgt gcatttaagt ttgtctgtgc 1740
gatagcatcc aacggcaccg ccaccagaat ggtcgatgcg agatatgcag ataattggag 1800
aatatgcatt aatttctact tcctgcgcgc aagctttgct tcaccgcagg tgtcagaaat 1860
cagggcgcaa gctccctgtc tttgtcccac ggcaacattt cacaatgtca ccgctacgga 1920
cggccgcgac tgaacacccc tcgtgtcagc catgggtgac tggatacggc aggtctcctg 1980
acttccgggt cttcatcggt cctccgcctt cccgaacacg aatgctcagt ggctataatc 2040
gtaagatacg atcataggag gatgactctc cggttacagt tgcgggggca gtctcggcat 2100
cagcaattta atgcttcacc gtgttccctt ttcatccacc ctctcgggca gaaccgtttc 2160
ctgaagcgag cgatagcaag gggaaggaag attatcaact gcaacaatgt gccccatctg 2220
aatcacattc agaacgaagt gattcagatt gttgaattgc aaaggttttc ctatctcaag 2280
aaatcgcgga agcgacgcag cgcaaagaag aaaagtacac tgccwattac aatcattgcc 2340
agcaattgcg gccacacaac actgagccct gcaccacgaa acagcaccga ttgtgccagc 2900
atcacaaaat gcgtattggg tgctgccaac ataatgttct ggatgatttc tggcatgctc 2460
tygcgcggtg ttgtgccacc cgatagcact tgcagcggca gcagaaccaa catcaacaaa 2520
aggccgaact gcggcatgga accggcaatc gttgcgagaa aaataccaag actggtggtc 2580
gcaaaaagct gcaatgcagy ccctgycaga aacagcgtca gtgaaccgtt gatcggcacc 2640
gccaagatac cctgaaccac cacgatcagc gaaaaggccg tagcgaccaa caccaccatc 2700
cccatcgacc ataccttgga gaccatgatc tcaagcggcg ttaccggcat caccaacaga 2760
tgctcgatgg tgccatgctc gcgctcacgg ataagggctg cacccgtcag aataattgag 2820
agcatcgtta ccgacgagat cacgttggtg atcgcgccaa accagccctt gttcaagtcc 2880
tgattgaacc tcgcacgcaa attgaggcca acgggcgttt gcgtgtcttc gcgatagcga 2940
ttgagaaact ctgtcacttc gcttgacaca atcgactgca catatccacc gcccgtaaag 3000
gcctggctca tgcgcgttgc atcgacgttc agctggattg ttggcgaacg tccagcgagc 3060
agatcacgct ggaagttcgg cggaatatcg agtgcgaatg tgtcaagacc agcatccatg 3120
cgcttatcca tctcgtgaga cgagataagt tttggcggca cgaaatatgg cggataaaac 3180
gcggtcgtga -tccgacccga aaccggcgac tgatcctcat cgacaatggc gataaccgca 3240
ttgttgaggt tttcaggcat agccttcacc gccgtataga ttgcgagcgt gaaggcatag 3300
acgatgagaa gcagaagcat cggatcacgc gctaatccgc gcagttcctt cacaccaagc 336C
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
tggaaaatat tggaaatccg catctcagcc cgcctgtttc ttgaggagaa caatgccgag 3920
aacagtaagc accggaatcg caatcagcag cggcaggaac gaccccgcca gatcggaaaa 3480
atcgagagcc tttgagaaag tcccgcgcga gatcgtcacg aaataagttg tcggataaat 3540
cttcccgata aaagcacccg ccccttgcag cgactgatac ggggtcgata atgcccgaat 3600
attgcacagc aggaatgagc gtcagcaatg ctgtgccgaa aatcgctgca atctggctat 3660
tgataaaggt cgatatcact aagcccatgc cagtcgtgat gatgacatag agcagcgctg 3720
ctgtggcata ggtcaggaag ctttccggta aatggcacgc ggaagatgaa gaccgcaaag 3780
gctgtcagca tcaaaaaatt gaggaaggcc agcgcgatat agggcaactg cttgccaagc 3840
agaaactcga atttcgtgac tggcgtcaca tagaaattga tgatcgaacc gagttccttc 3900
tcgcgcacca cgctcaacac cgcgagcatg gccgggatca tcaaaaggag aagcggaata 3960
actgctggaa ccatagccac aaggctctgc acgtccggat tatagcgata gcgaatttcg 4020
agattgaaat tgccaacggt agcagcgttt ccataaagct cgcgcgcctt ttgcgtcatc 4080
cagttggcgt gcatgccctg tacataacca cgtacggttt ctgcacgcgt cggcatcgca 9190
ccatcaatcc aggcccccac ctcaaccgga cgaccacgcg cgacattgct gccaaagttc 4200
ggcgggattt caatcgccag gctgatctcg ccttcacgca tccttcggtc aagttcgtca 4260
tagtcggtaa tgggagactt ttccgtgaaa tagcgcgaac cggcaagctg ctgggtataa 4320
tcccggctga tcgtggtgtc atcgcgatca agtaccgcaa atgtcaggtc ttcgacgtca 4380
agattaatac catagccgat gacgaacata agaatgacag taccaagaat ggctaatgtc 4440
gcacggatcg gatcgcgctt gagctccagc gcttcgcgcc tagaaaatgc gagcatccrc 4500
cgaggattag gcaaccagct tgatgaaggc tttggattct tcaccggctt cttttcgggt 4560
attggatcag atttttcctg attactcttc tgcggcgcag tctcgcctat cgcttcttcg 4620
agataggcaa taaaggcatc ttcaagcgtt gccgaactgc gactttctgt gatcgccttt 9680
ggcgtgtcac tgatcagcac cttacccgca tgcatcagcg aaatgcggtc gcaaagctcg 4740
gcttcattca tgaaatgggt cgagacaaag atcgtcacat tatccttgcg cgaaagatcg 4800
gcaagtatct gccaaaatgc atcacgcgca acgggatcaa cgcccgatgt cggctcatcg 4860
agaatgagaa tatcaggcga atgaattrag tgctaccagg ccaragmcag ggcgctgscg 4920
aatgccaasc ggcatagact ctggaagctc atccataacc ccagccaaat caaaatgttg 4980
cgcgagttcc ttgattctgc gctgggtgtc ttccgcattc attccaaaga gctttgcgtg 5090
cagctccagg ttctgatgta ctgtcaattc tgaataaagc gaaaaggctt gcgacatata 5100
accgacacga cggcgtatat cgatatcctt gggatcgacc tcgcgtccaa acaaccgcgc 5160
tgtgccttca ctcgctggca aaagtccggt cagcactttc atggtcgtag atttgccaca 5220
gccattagag ccgagaaagc cgaaaatctc accgcgcgga atgcggaagc tcacattatc 5280
gacagcggta aaattgccaa accgcacagt gacatgctca gcttcgatag cgatgccgct 5340
atctgcctca gcattgcgcg acgggcatca caaacctctt tgtgcccttc ccgtaactcc 5400
tccggcaaac aaagcaataa aggctgcatc gagattgggc gtctttgttt gttcaagcag 5460
ttcctgtggc gttccggtcg caagaattgc gccatcattc atcgccacaa gccaatcgaa 5520
gcgctcggcc tcttccatat aagccgttgc cacaatgacg ctcatgcccg gacgatcttt 5580
gcgaatatcg tcgatcagct cccagaactg acgtcgtgac aaaggatcga caccagttgt 5640
cggttcatca aggatcagca aatcgggatc gtggatcagc gaacagcaaa agactggttt 5700
tctgcttcat accgcctgaa agctttcccg ccggtcgatc cgcaaagggt gacatccccg 5760
ttcgagccaa aagatcggct atacggcgtt cgcgttcatg cttgtcatgg ccaaataagc 5820
gaccaaaaaa ctcgatattc tcgaacaccg aaagtgtcgg ataaaggttc ttgcccagcc 5880
cctgaggcat gtaagcgata cgcggaaaaa ccgactcacg atggcgcttg ttggagatat 5940
cgccacccag cacatcaatc tttccctgtt gcatggcgcg tgcaccagcg accagtgaaa 6000
gaaggctcga ttttgccgac accatcgggg ccgatcaggc cgaccatrca gcctgctgga 6060
acatcgagtg agatgctatg aagtgcagca gcagacccgt agggacagcc ctacaccttc 6120
agcgcagacg acaaagctac cgtcttccac accagccttt atcgaggccg cactcatttt 6180
acggtttccg cgaggttctt cggccattca gcattcgcat caagcttgac gtaagccatt 6240
16
CA 02282858 1999-08-24
WO 99/34019 PCT/US98I27744
cctggcaggc cagtttttac ctgctggatg tatttttgca gcaaatcctg tgggattttt 6300
gccttcacgc ggaacatgag cttctggcgc tcttcttccg tttcaaccga cttcggcgtg 6360
aactgcgcaa catcagcaac aaagctgatc gtcgccggga tcacatattg aggtgccgca 6420
tcgagcacta tgcgcgcatc tgccccaata gctacacgac cagcctgcgc agtcggcagg 6480
aagaacgtca tatagacatc gctgacatcg accagattaa gcacgcgacc accggctgac 6540
agcacctcgc ccggttgcgc aacgcgatat tgtacgcggc ccggctttgg cgaacgcaag 6600
gtggcatcgt tgatatccgt gtcgattgtc gcgatggctg cctttgcagc ctcaaccgcg 6660
gcttcagcat cgaccacctg cgccttggca gcactgatcg cggctgcggt tgccgcaagt 6720
tgggctttgg cggcaccaac agcagcttct gcaccttgag cggttgcgcg gtcatcatcg 6780
agcacctgct gggaaacagt gcgcgattcc gaaagctgct gtgaacgaac aagtcgtcgt 6840
tgggcagcat ccaattgcgc ttcgcgttgc gcgacggttg cttccgcagc agtttgttcg 6900
gcttcacgct gggcgacgag acttttagct gtatcaatgc ttatttcagc acggcgcagt 6960
tgtgcttctg cctgtttgcg ctgactttca agctgagccg tatccatccg ggcaagaatg 7020
gcattcgctt caacgaattg accttcatcg ggctaggatt tcgcggatgc gtcctgggct 7080
tttggtcgaa acgtcgatct caacagcttc aatacgtcca ttcccgcctg caataccatc 7140
cggcaaaccg ggatcgctca atgtcttcca ggcatagtag cctccgacgg ccaaagccac 7200
gaccacaccg gttacgatcc actgcttgcg attaaatccc atgccgaaat atcctctgcg 7260
tcatcatctt gcggacccgc acagctaaat tatgcggcaa atgattttat taaatcagac 7320
tgagttcagt attttcactg aggcgagatc gccttgatta aaatcaacta tactcaaatg 7380
catcgcagtt tcatgcgata aataacaata aatataagaa agttcgcggg tgccgattta 7440
gtgagatgga gggcaatgct gacagcaccc gctgactgtc gacagtacaa cattgcaaaa 7500
gatcgcgctg gtgcgctcga cagatcccta aacaacttga gatttaattc ggaaagttta ?560
gccgggacgt cgctttaggt tgggcctcga cgtcccgggc tgtcagttct ggtggaacct 7620
gacaacgagc gatcattagc acccggtcat gaccgctttc tttgatctaa atcaattaga 7680
taataattat atgcaatcac acccactatt ttggtgagcg gcacttaccc cagctcttct 7740
ttagatagga cgatacgctt ttaagcttgg gatcagacaa aaagccctgc cgaaacagaa 7800
tactgccttt gacctctggg atcgcgtcat tgatatcgag ttggcgtttg atttcgtcca 7860
cgccattgcc ggcaccccat tccggctcag acttcgcaga agtacccgcg cgataaagcg 7920
ccatgccgat ataaagatcg gtctttgtgc ccttgacggt atccgcccac catttcacga 7980
tagggccata gggcacatct ttacgccctg acgaccaata gacctgcggc gcaatatagt 8040
cgatcaggcc gtctctcacc cagacgcgtg tatcggcaaa atcaccatca tagttggttt 8100
tgcccgcccg cgtcggcgaa ccgcgaggat catcgatctg attgcgccag acgccgccgg 8160
ggctgatacc aaagcggaca tgtggcttga tcgctttgat cttgtgcgaa atttcctgca 8220
ccagcgtata ggtattgtag cgccgccagt catgtttgct ggagaaccgc gtcccaaaac 8280
gtttgaatgt tttgtcgtct ttgagcggcg agccttgcgt ttcgtaatag aaatagtcat 8340
cgaactgtat gccatcgaca tcatatttct gaacgacttc ggccgtgata ttcgtcaccc 8400
actggcgcac atccggaata cccggatcaa gcacataacg atccgcagat atagccaccc 8460
agcctggatt ggttttatag acgctgggcg gagaatcgcc ggcagagttt ttcagttctt 8520
tccgcgttgc tggtcgcaca tccatcgaaa cgcgataagg attgagccat gcatgcagct 8580
cgatcccgcg cttatgcgct tccgcaattg caaagcgaag tggatcgaag cccggatctt 8690
ttccgagcgt acccgtgaga taagacgacc acggcagata ctccgattta tagaaagcat 8700
cggcagcagg agagacctga aaaatcatgg cattgatgcc atgctccgac gcctcatcaa 8760
acatccgcac cagctctttt ttctgacgct ttacccgttc ggaatcatct tcaatgagag 8820
tggaagcccg cgacggccaa tcgagattaa garcagttgc aacccagctt gcatgaaacg 8880
tatcgcaatc aagtggcatg gattacagaa ttcwhawha* ywvtsrnm*y wvtsrnmkhg 8990
*khg***dcb a***dcbanr mamhadatar agrahnth*w hnmartndat nstathbcdc 9000
ggmgtmsnwr mansymbara hbcwhnmart nwhnmartnh ddtbcbwhnm artnnrmawh 9060
nmartnmcrs twrddhccdb bcttdgdanb bdcdaa*rtn tryatabwrd dcmnthsmma 9120
17
CA 02282858 1999-08-24
WO 99/34019 PCTNS98I27744
rynrmatndc mntsmmaryn rmatnhcmbh hhhmcrstwr ddcmntmswr ddcwrddcmn 9180
t 9181
<210> 16
<211> 7312
<212> DNA
<213> Stealth virus
<400> 16
g*bbmavbcg aattcgaaat tgacagactc gtcgctgtcg ctctcttcct tggcgtcgtt 60
aaagtaatta gagtttctat ccccggggtt ggcacccccc ttggatgtta agtaattggt 120
gatcttgtgc tgatcgtact tttccttggc gttgtggtcg tgttcgttga tttttcgtgc 180
ggacatccgc tcgtgcttgc gacccacggg ctcggggagc atctcgctgt ccattccaga 290
cacgtcatcg tgcaaagcgc ctgaatttgg gaccgctgct gccctctgct gcttgaaatt 300
tttatcgaag ctcaaatcgc cgcgctggaa cggctcctcc gtgaggaagt tgtccacgca 360
gaagagaccg ttgtggctgg acacgtgcaa caccgtatcg tgctccgtga cgatgcggac 420
cgtgcacggc agcttggtga ccgcgcaatt catcagggtc tgatacagat tcttgagttg 480
tacgtgcacg cgcatatttt taaccccatg aaaactgact cgagtgttag ccgtgaactc 540
cagctcgctg ccactgctga ggatgaattt tatagccgga ggggcagaat gtaccagaat 600
ctgaattgtg cccgtggggc agggagcctt tttgacactg cgtttaacgc gcgtgtgagg 660
cgagatccac ttaatgagct cgctcacgac gccatgatcc aaatcaacgt gcacggccga 720
actgtcactc tcacgtacca aatcttggct gtgcacgcag ggcgagctga actccatgtt 780
gaaatctggg gcgcacatgt gaattttagc ggacaggtca gagatatctt gcacgtaaaa 890
cttggttaag tccttgctag aggtcaggta cataaagtta cccagcatgg gcgtggaatt 900
gttaatggtt ttcggctgaa acgacttgtc ggtaatgtac agacaggagc tgttgaacgt 960
gattttagag acaaactggt tgcgtaccgt ctgcaggacc agagcggggg tgggcagaaa 1020
ggtcacagtg gtgttttcct ttaaagtacg aattaccgac cgcaactgct gaatggccga 1080
cttatacggc ttcagccgca gcgccagcgt gggaggctcg ggtaaacggg cttttctctc 1140
catgtctgcc acgctcctga gacccgcagc cagctcctag atgtgtcctc gtccggaacc 1200
aacagtcaaa taagcctaaa cgggttaaat aattgacttt tatagaggac ggacggtgcc 1260
gcaaaataac cacgctgaaa gtggaacgat tgcagcacac agcagggttt gatagcgttt 1320
aatacagctc tggtaatatc taggttagca cacaagtccc atctagggag cacagtactt 1380
atatactcca accttacagc gcaagtggta ccatttcaac atcctcttca tcagatcatc 1440
gggggtcata gagggctcgt aatagaaagg caacgtgaga cactggtcca catacatact 1500
catgttcaca ctggccattt ctacgtcgga atgcagttcc gcggcccgct gaaagacaca 1560
atcagagacc tgcgaggggc gagcgctctt ggatttgagc tcgtcctggt gctcgatcca 1620
agcgtaattc acgacgggga ctttcaagtg tctctgcatc acagtgggga aataacagtc 1680
ctcggtgggt ggactgatgg gcaaaacggt gttctcctcg acgattttgt cttttgcggc 1740
ccacaccgaa ggggttacac tccacagatg ggcaacgtcc tcgtcgggac cgatagccag 1800
aaactgcaca ttgcgcgacc cgtattgttg catctcagtc cggagggtct cccactgcgt 1860
cgttgggagc gacagccggg gctttcgata catttcaaaa ataaacttgc cctccttgta 1920
gatggtgcga tcaaaccact cgcagggtgg cagaccggac ttacacaggt ccacgctggt 1980
gcgcagcgcg gcatagtaca tgttttcaaa aaccctctca attaagtccc aggaggcgaa 2040
ataggtaaac cccagacgca ttaacaccgt atgcagaccc actacaccga ggtttaaacc 2100
ccgcatttta gacaaggccg actctacagg ccagtctcca gccgtaatca tggcatcgag 2160
acgcccgttt gcccacacca ccgcctcctt caccagttcg cgaagcacct gtaggtcaaa 220
ataacgcttt gtgtttccca aaatcacatc ggacctggga agcgcgtcct tgtcactacg 2280
ggtgaacaaa cagcgtgcca gattgattga cagtcgctgt atggggatat cggcatccac 2340
i8
CA 02282858 1999-08-24
WO 99/34019 PCT/US98I27744
aaagtgacag gacgccatat ctggactcaa acatggcggc aggggaatct ggcccattaa 2400
cacagaatat ttcaccacgt tatgcacaaa cactatagca cacttcccct tcagggcaca 2460
gaacagcatg tttcgtaaga agtcactgga tttcacggtg actttggccg aagactgctc 2520
atagcgcgcg tactctctgt caaatgtcgt ttcgtttccg tgctcagaca gtttcctaga 2580
gatacaacgc ccgaataggg agtagttatc atcgtgggcg cggtaacgct tcatgagtat 2640
tcccggaacg ttaaaagcaa agtacactcc acatatggag gtctctttca ggataaagtt 2700
gagaactcga atggctgcca cgtcccacag gtccacaaaa attcgcacga taggcttgtg 2760
tacctctctt tcgcggatca tgtcacagaa accgcctata cagcgaataa cgctaacggc 2820
ctccacgttc aatcgggtga cattaatgga caccgacacc ccacgagtga gattttcgta 2880
cagycatttg tgcaaggtga cccagtccac atcacgagaa aacatatcgg aagacatgag 2940
gtagtcatgc ttaggcatct ccacgaagcc aatgttggac atggcaaaag gcgttatgga 3000
cagctgtccg tctcgacatc gcctgaggac attttccaac acctcaccct cgtgcctaca 3060
atcaaggtgg aaacgataca cccgggaaca agggctgttc acgatggctg acgtgatacc 3120
catcgcgttt cggagaaaag cgccccctag tgattcatct tgcccataca tctggcgaca 3180
gatggtgtcc gacaacaaga tggcggaata aaaaccccaa cagccggcca gatcaagata 3240
gcgattggtg tcctccaaaa gtttaggcag ttcttccgaa tgccgcaaaa caaagtcgcg 3300
tagatgttca tcgcacatcg aagaagtgta cgacatagcg cttcgatttt ctctcaccca 3360
gttgattttg agataaaagc gacccataag aagatccgaa cggggaactt gtttaatcaa 3420
accgggcccg aatcttatca acatctgaaa gaggcgatac gcgcctctga tgcccgtctg 3980
gcgtgaaacc acatcgatct cccgccacgt gttggcgcga tcctccacct gtttgacggg 3590
gtccggtaca tcgcaaaagc gaaatttgcc ccatcgaccg tgacaatgac acttctttcc 3600
catcagcagt tgcacagtgt tcatccccgg catatgggcc gctaacgaac aagaagctcc 3660
cagcctgagc gttcccccct cgtctccagt agaccagcga gccgccgcaa caccgatcgt 3720
cggctgcggt tgactttttt cttcttcaga cgaaactgtg gtgtccatag cctccccatt 3780
ctcactcgaa gcctcggatt cctccataat tgttccgagc cctacgctac cgttcttgtc 3840
ggacgcgtga gccatagcgc ccgataatga ttaaacgaac tctgcgaact ctcccagttc 3900
cacgttgaaa tgatccaaac gcaccgtcga caatttaacc tcttggtgcg tcacgacaga 3960
ggtgtgaatg tcgtcgtaca aacaccaacc cagtttctga ataaccccgg tacataagga 4020
gatgtgtcgc ggcctcgtga tccgcttgtt cacaaaagta cagcgctccc gggtgaattt 9080
ttgtcgcact acgtccgtca aggtgtggcg attaccgata ctcgacgtgg ccacataaat 4190
tgccacctta gtttccaagc cctcgtggtc gtaaacaata attaaataca catattgcaa 9200
tctctcctga gtttcttcca aacacatgta catgtccttc ggtatcgata acgaaaaaat 4260
ctctgttttt aacgtgttgt atatgtagcc ccgtaaaacg caggttagta acgacgtgat 4320
gcccagcgac accgacttca cgcaaccaat ggtccgaaga cgatgatgta agagcttact 9380
gcccatgtcc aaccaggtca aggcggcctt ggccggccct gaagtataga tgccctccag 4440
ctggcacctg gcgcccaccg acacgttaga ggccttgatg gccagcacgt acaggctgat 9500
gtacaggtac cgcggcgact cggcgccagt ttccatacga aacatgagag atccggggtg 4560
cacctcaaat tccaccagac cttctggaac aaaaaaccgc gatgtgatgg cctggtgatc 9620
cgcctcgtac aggtaatgga ccgctagtgt atttacttcc ctcttcaact tggtcgccag 9680
cacgagttcg ttatcttcat cgttcggatc cctcggtcgc ttggcgacat cgcgcacgtc 4790
catgatgagg aaacgcacgg tagactttca gtggcttttg agcgagctaa aacgacaatc 4800
aacggagact caggccgtgt taaatatcct aagccaaata gagatcggcg cactcaatgt 4860
tgagaccgtc aacgccacta aaatacaaca gttcctgcag cttttaccgc ggaaaggcta 4920
tcacttcacc ttcatccagc aaaatatcgt ctactacctg mttagtcaca ccacattaca 9980
aaccgccagc gatcccctca tggcggctaa aaacttctac gaagagataa aaaaacacgc 5090
cgagagacac accgtcacca gtccctgcga gtatctcaac aaccaaacca ctctcacgca 5100
cttggaaaca ttcctaacca aagtgcaaga actgcaggct tcgttcagca ccaaccaatt 5160
cctagccgcc actctaccgg atcaaaagag caaaaaaaca tcacgggata tcagcgacaa 520
19
CA 02282858 1999-08-24
WO 99/34019 PCT/US98I27744
tggcacgcag tacctcatac gaagcgtgtt cacgcagatc gaagaagccg tagaaaacgt 5280
gcgaccgttc agtaactgtc gtttcatcgc agaamtgctg gacatgctgt atcacagcac 5390
gctgcaatgg tccagtggat taatgcagta tcacgcgttc gcggaagatg gtgacggcga 5400
cctagacaag atcctcaaga tgtattattt ttacaaatac tatcaagccg ttaacaacga 5960
cctcaacagt gagtttcaaa cgttcattac tagcgacaaa cggaatctca gcgctttcat 5520
tctctccgac gcggatggag accagcagat tggggcagaa cacattaaag agttgagttt 5580
taaggtgttt aacgccaatc taaatgaccg cgacacgact ggactcgcgt ttcccataat 5640
tatgaccacg ttatctgtct taaatcacat gtcggtggaa aatatgtttt accatccggg 5700
actagtgttc agacttgctc agtgacgaat ctgaactcag ctccagcgaa catacccgcc 5760
tcgacttagt agcacaaatg tgcacccata tgagcggcga atttttccgc aacaccacca 5820
aacccttaaa actgcgagac ctcatgtcgc gtatccaaaa attcacctct ataggactga 5880
accgagaaac ctcccgggcg tatgcccaga tggcacttct ccaacccagt cgaacggcac 5990
ccaagaaggg aacagaaatg tggtttgaga ttcgacagca actgctcgtc atgatttaca 6000
acacatatgt gtttttcatg tgcctttggg tgtacagccc aacgttcctg ttcatccata 6060
gacggaagat gattctggaa caacaaaaat ccacgctgat cggatccaga cacgaactgc 6120
agttcatctg ggataatgta acacataata tcaaccacga ttttaatgtg atgtttaccg 6180
aagatgagtt taacgtgtgc accaaaggag ccacacagct ggaaaaagaa tacctttacc 6240
gcgacttgct gaacaaatgg ggtgacatcc tgtttgtgat gaaaaccaag ttaaaacctg 6300
acgcggaatc acccactctg gacaatgtaa ccaccgccga tgttattaaa cgttgcgcta 6360
tgatcaatct gtctgaaacc gatgtgccct acgaatcgtt actacccctg actcaccatc 6920
ccagttttct cgacacgttt gtcaacttag ttattgttcc ggagttttca caaatcctca 6980
acatccccta cacccaattt ttcaccgtag ggtctcctcg tctcctaaaa ctcattcacg 6590
cgtgccgtct gctagtgccc gatcagataa ccttatataa caaactggtg tccctctaca 6600
acctaaccac ctttgtgtct gagattgacg taggtgtgtt ccgcacagtg tacaccctga 6660
ctttggaaat cgccgcgata ctggagagcc tctgcggcga acctgtatct ccagaattag 6720
atctgctagt agagctaatg gctcaatcgc tctcacacaa tctagaaact acagtcaacc 6780
cactaatcga agaagtaatt caaaacaaca gtgcaagtat tgccaaatat ctagaccaca 6840
ctcatctgtg ttattgtttc gcacaaacca caggacagat gtccccagat atggcaaacg 6900
tggaaatcac cctagagtcc aaggtgatcg ctaatatacc catgactcag tttctgcaac 6960
tcactaaaac tctcattgat aaagatcaaa aactaatcga taatttctct agaattc*vn 7020
g**ywvtsrn mkhg****nr mamhadatar agrahnt*** **whnmartn datnstathb 7080
cdcmbgtmsn wrmansymba rahbcwhnma rtnwhnmart nhddtbcbwh nmartnnrma 7140
whnmartnmc rstwrdmmdh ccdbbcttdg danbbcdaa* bcdghkrtnt rywvvmtabw 7200
rddcmntsmm arynrmatnd cmntsmmary nrmatndath hadcmbtath bcdcddmwst 7260
athbcdcdat nstathbcdc wnhhmcrstw rddcmntmsw rddcwrddcm nt 7312
<210> 17
<211> 2103
<212> DNA
<213> Stealth virus
<400> 17
*gbbsmbcga attcaacatg gataggattt tctgtgtaaa gacctgttga aatttttcca 60
ttttttaaga aaagtaattt cttcatcata tcttcagctt tgtattcatg agctacagcg 120
cctaaaatac cattaccata tcagaagtct tggaatctta aaaatgcacg accttgtttt 180
actaatttta gtaatgtatc attttcaggt ttagctaagt cttttttaac atctgctaaa 290
gattttgttg aagcaactat aacaccttca gtgttgtgtc taataccaaa aagtttttca 300
gctggtaatt gagtaatttt ttcaataccg actactgaac caaatgatct aagttgtttc 3E0
CA 02282858 1999-08-24
WO 99/34019 PCTNS98/27744
ttttcttctt cagttgcttt aactttttta gcaatacgat ctaataatcc tggtgaaaat 420
tgatctaaat cagcaactgc attagatgca actaaagttg taattctatc atgtggtgca 480
taaaaaatat ctggcacaat tttttcatct gttgcccctg taggcatttc taaagcacct 540
caaacatctt tagctattgt tttaatttca tagccatttt ggcctgattt tgttttctta 600
aacaattcaa ttgctttgtc atagaatttt tgttgaacgc catcaactgc aattaaaatt 660
gtttctgctt tcagtagtac cacaactaat tgtagctaat gctgtcactg gagctgctaa 720
ggttgcaaag ccaattgcta tttttttaaa agttttctta aaattactca taatttctcc 780
ttgttagcta actattcaaa aacgattaga tttttttcat aagcaactat tgaaaagata 840
attgctagtg gactaaaaaa agttaagaca aatattgttg caataattcc gcttcatttg 900
taaaattcgg ttttatccaa aatatagtaa acatgaatgc aaacgaatat tgcaaatata 960
taagaaagta atgcagctga aaataaaatt ctataagtat aactttttat ttcgctaact 1020
atgttttcta aatatttgcc ttcaaaagtt catttatttt tgcctagtaa atacaaaatt 1080
aatatttcta aaatcaaaat aatgatttga gtaaaaacta ataacatgta ttcaagaatt 1190
ttaggtaatg atcttctttc atttggtcat ttgcctaaaa aaagtcatct cattctagtt 1200
ttaaatgaaa cttttgtact ttttttgttt tctaatctcc tgtttttttg cataattaac 1260
taaataaatt atattttaaa attaaaatat atgccttgtc agtgtgcaat tcttgattaa 1320
atataggaac attacccttg accactcaag ataataaaaa attcaaaaaa caacaaattt 1380
tagtgtaaaa aatttctttt tgctgttttt tgtgcatttt atatattctt attcttaatc 1440
taacttaatc taattgtgga aattttctca tatatgagat tttaattttt aataagttaa 1500
ttcaactaac attaaaccag tattcccact aaaagttatt ttttcattgt ttatcgaaga 1560
attattagaa aaaataacat taattttagt tggagcattc ttaaagacta gatttcattc 1620
ttgaccataa gttgtatgat aataaattga attgactaaa actaaaaact ttttatcttt 1680
ttgctttgct ttaactaatt tatatccaag tcctttataa tcataaccgg gtttaaagag 1740
atcatctaaa ttagcataag tattttcttt ttcagcaaac atttttggat tttctttacg 1800
ataattaatt atttttttgg ctaaattaaa attagatttt ttattcttat gagcttgttc 1860
aatcgaattc vngnrmamha dataragrah ntwhnmartn datnstathb cdcmbgtmsn 1920
wrmansymba rah*bcwhnm artnwhnmar tnhddtbcbw hnmartnnrm awhnmartnm 1980
crstwrd*dh ccdbbcttdg danbbdaart ntrytabwrd dcmntsmmar ynrmatndcm 2040
ntsmmarynr matncmbdat natnatnnda tnatnmcrst wrddcmntms wrddcwrddc 2100
~t 2103
<210> 18
<211> 3169
<212> DNA
<213> Stealth virus
<900> 18
gbbsbcgaat tcaagggaac gaaagcacgc cctgctcgtt ctaagaaaat tcgcggctca 60
tggaggcttt gatgagaaac gtcgacagga aagatcgtct gatcctggcg ctcgcagcgc 120
tgctgcgtgc tgaacgcgaa acccgtggcg ctttggaagc agcactgcaa aacgaaagcg 180
tcaacctcga gacattacgc gcgatcctgt cggatccggt cccagtgatc acagaggacg 290
acatcgcatt tgccgagcat tttgcccgct caagacatct ccctccgttt cacctttcaa 300
acgagccgct cagcacagcg aagccaacgt cctgacgggt aagggtagcc gccaatcgct 360
ctccagcggg cggaaaccct gttgttgttt ggtcaaaaaa cgctaatctt ccgatatctc 420
gtgtttgagt ttgtttcaga atttcccatg cggagtgaat tgtgagcgat aacaaaattg 480
tgcagggtgg agccgcgcct ttggtctcca acacgcatgc ggcaagtccc accgcgcccg 540
ctgtttcccc ggactgccgc agcttgcttc ggacaatcga ctggccacaa aatccactcg 600
gcccgattga tagctggtcg cctgctctgc gttgcgcact ggatctcgcg cttccggccg 660
21
CA 02282858 1999-08-24
WO 99/34019 PC'T/US98l27744
acgctcagat tgtcattttc tggggacccc agttcatcgc gctttataat gacgcctatc 720
gtccgaccat cggtcacaaa catcctgcgg ccttcggtcg accggcccag gaaaactgga 780
cagaattgtg ggatgatctg aaaccattgc tcaaaactgt gctcgaaacc ggtcaaacca 840
tttccgcgca gaaccgccct tttcacatcg agcgcttcgg ctatccagag accgtttatt 900
ttgatatctc ctattcgccc atcggcgcct ccgaaaacgg agcctcgggc gttctctgca 960
tcgtcaatga aaccacatcg cgcgtggtcg cgcagcgcaa gctcactgaa aaccagcagc 1020
ggctggaatt gcttttctct caaactgacg cgggaatagc actgagcgag cgcaccggca 1080
ccctgatcaa ggtcaatccc cggctctgcg cgctctccgg tcatagcgag gaaacgctgc 1140
gcgctggcgg gctcgatgcc gtgctcgatc ccgcagatca agaagcttat caggtttcac 1200
ttagagcgct gttcaccacc ggggaaagct ttctgcaccg attcagcctg gtcggcgcca 1260
atggtcgccc aacccccgtt agctgcgctg caagcccggt gcgcgacgac accggtgcta 1320
tcacgcatgc ggtctggacc attatcgaca tcaccgaaca agtgcgtgca caggaactgg 1380
aaagtcagtt ggcggcaatc gtctcgtctt cccatgacgc aattctgagc accgatctcg 1440
aaatgcgcat tttgagctgg aaccacggcg cggaacgtct ttatggctac agcgctgccg 1500
aggccatcgg gcgcaaagtc accatgttgc tgccatccga cagaacgacc gaagaggtcg 1560
agatcatcga taagatctcg cgcggtctcg ctgtcgcacc gcatgaaaca gtgcggctgc 1620
acaagaatgg tacgcgactg gatgttcagt tgacggtatc gccggtccgg gatggcaatg 1680
gacgcatcat cggtgcgtcc aaaagcgccc atgatatcag cgaccgaaaa aagtccgaac 1740
aactgcagcg cgctattctg ggtgagatga aacatcgtat caagaatgtc ctggccaccg 1800
ttcaggcttt ggcacgccag acatttcgca atcccgctca taaaagcgcc tatcaaacct 1860
ttgaagcccg attgggcgcc atggcccgca cgcacgatct tctcaccgcc gatgtctggc 190
aggcgaccga actcagtaaa ctggtcgaag aggcgctgtt gccattcggt ctttccaatt 1980
ttgctatcaa aggcccggag atcgacgttt cttcacgtgc tgctatggcc ttttcgcttg 2040
gcctgcatga attggcgacc aatgcgtcga aatatggtgc gctttcagtg cagggcggct 2100
cagttcacgt cacctggtcg cacgatcaag cgttgcagca cctgaatttt gtctggcagg 2160
aaaaaggtgg tccccgtgtc ttggtgccca agagcaaggg tttcggtagc aaactcatcg 2220
agggcgtgct ggcgggagaa atcggtggta gcgttaaact gagttatcgt tccgacggtt 2280
tgcactgtca ggtcagcacc aagatcgcca atctcaccca acaaccgtaa actccaccgg 2340
cgacaacacc tcaggccccg cgctcacgca ttgatcggcc cattgccgcc cttgcgcatc 2900
gcctgacaaa gcgggatgcg tgctgatgtg ggtcgcagga ccatagggca cctcagcttc 2960
aaaccggcgc cgcgatattt cttcagaaaa agaattgagg gcatgaaaca aagccgccgc 2520
tcggcggttc ggtccatatg cgcatgcaac aagcatggcg caactacggg caattcaaca 2580
gaggagccgg aaaatggcca aagcaaagca acgcaatctt gatgatctgt tttatgacac 2640
gttgaaagat atctactatg ccgaacgcaa gattctgaaa gcgcttccaa aaatggcgcg 2700
ggcagcaagc gatgagaagc tgaaagcagc atttgaaacc caccgggaac agaccgaaac 2760
acatgtcgag cgcctgcagc aatgttttga attgctcgga aaacgcgcgc agggcaaaac 2820
ctgtgacgcc atcgaaggga tcatttctga aggcgaagag atcatggagg aattcctgca 2880
gcccggggga tccactagtt ctagagcggc cgccaccgcg gtggagctcv ng'nrmamha 2940
dataragrah ntwhnmartn datnstathb cdcmbgtmsn wrmansymba rahbcwhnma 3000
rtnwhnmart nhddtbcbwh nmartnnrma whnmartnmc rstwrdvvdh ccdbbcttdg 3060
danbbdaa~r tntrywnsta stabbcdcdd mwwrddcmnt datncatsmm arynrmatnc 3120
ddcmntsmma rynrmatncm bmcrstwrdd cmntmswrdd cwrddcmnt 3169
<210> 19
<211> 3878
<212> DNA
<213> Stealth virus
22
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/Z7744
<400> 19
gbbbbbbbby bcgaattcaa tttcactgag tctgcgttgg agacagcggg gaagtcgtta 60
cgccattcgt gcaggtcgga acttacccga caaggaattt cgctacctta ggaccgttat 120
agttacggcc gccgtttact ggggcttcaa ttcaatgctt gcacatctcc tcttaacctt 180
ccagcaccgg gcaggcgtca gaccctatac gtcgtcttgc gacttcgcag agccctgtgt 240
ttttggtaaa cagtcgctac cccctggtct gtgccacctc cacctagttg cctaaatgga 300
ggtcacgctt cttccgaagt tacgcgtgca ttttgccgag ttccttcaac gcagttctct 360
caagcgcctt ggtattctct accagtccac cagtgtcggt ttagggtacg gtctatatgc 420
aggagctatt tcctggaacc gcttcgctgc cagatcaatc caataagacc tgacaacaca 480
cgcaatccgt cactacctgc aggcccacga atattaacgt ggttcccatc gactacgcct 540
ttcggcctcg ccttaggggc cggctaaccc tgctcagatt aactttaagc aggaaccctt 600
ggactttcgg cgagggagtc tctcactccc tttatcgtta ctcatgtcag cattctcact 660
tccgatacct ccaggatgtc tcacgactgt cccttcacag gcttacggaa cgctccgcta 720
ccacgcacat acgtgcatcc acagcttcgg tgtatggctt tagccccggt acattttcgg 780
cgcaaagacc cttatttaga ccagtgagct gttacgcttt ctttaaatga tggctgcttc 840
taagccaaca tcctggttgt tttgggatcc tcacatcctt tcccacttag ccataactta 900
gggaccttag atggtggtca gggttgttgc cctcttcacg acggacgtta gcacccgccg 960
tgtgtctgcc cagtagtact ccccggtatt cggagtttga ttaggatcag taagacggtg 1020
agtccccata gcccattcag tgctctaccc ccgggggtat tcgctggacg ctctacctaa 1080
atagatttcg cggagaacca gctatctcca agtttgattg gsctttcacc cctanccaca 1140
agtcatcccg atctattgca acagatatgg gttcggtcct ccagtacgtg ttaccgtacc 1200
ttcaacctgc tcatggctag atcacttggt ttcgggtcta atccgacgaa ctgaacgcct 1260
gtcagactcg ctttcgctac gcctacacct accggcttaa gcttgctcgt cagactaagt 1320
cgctgaccca ttatacaaaa ggtacgctgt cacccagaac tgatcttggg ctccaactgt 1380
ttgtaggcat tcggtttcag gtactatttc actcccctcg tcggggtgct tttcaccttt 1440
ccctcacggt actggttcgc tatcggtcat gcacgagtac ttaggcttgg atcgtggtcg 1500
acccatgttc agacaggatt tcacgtgtcc cgccctactc aaggacttat gatcgttcta 1560
cgtgtacggg gctatcaccc actttagcca acctttccag attgttccac tttactcaca 1620
taagccactg gcctggtccg cgttcgctcg ccactactag cggagtctcg tttgatgtcc 1680
tttcctctgg gtacttagat gtttcagttc cccaggttcg cttctaaccc ctatgtattc 1740
agaattagat accttattac gataactaga aagttgaact gttcttgctt gcgcgccaac 1800
aattcaaatt ttctagctat ctaaggtggg ttgccccatt cggaaatcgt cggatcaaag 1860
ggtattcgca cctccccgac gcttatcgca gcgtatcacg tccttcatcg cctgtgcatg 1920
ccaaggcatc caccaaatgc ccttaagaca cttgatcact ctcattgcca atatccatca 1980
aaacatccgt cttgattata tcagcagaaa gaccagcttc tcgagataca atcggtggag 2040
cggttaggcg tccaatcata atgcaaggct tgagcaagct cttgcgacat tagccaaagg 2100
ctaatccgat tacatcttct cttcacgatt tcatacagaa caggcaaatt gctcaaagca 2160
atctgcaaac ttgtttcttt cttttgttga atgactacaa tccgtcctac tcgacaccaa 2220
aattgtgatg gtggagctta tcgggatcga accgatgacc ccctgcttgc aaagcaggtg 2280
ctctcccagc tgagctaaag ccccttatca catttatcaa agcaaagctt tgcaaggcca 2390
agcggccgtc gcagcccatg ctgcgctcac gcgaagtgcc agcagcgata gctgcgatac 2400
ggcacgtgag cgataatttg gtgggcctgg gaggacttga acctccgacc ccacgcttat 2460
caagcgtgtg ctctaaccaa ctgagctaca agcccctata ctatcgcatc cccatcaaga 250
gggcgccaat acaggacgct agtccgtcgc cactcgtgtg gcgcgctcgc gcagggccag 2580
cagcgttagc tgcgatacgg cccgtgagcg ggtcatgtca atcaacaatg aagaaagaga 2690
aacgaaggcg gcacgcctgc aaagcgatcg tcagagcgac tactctgcga tctatgttct 2700
aataagcatg agaaagttca tccacaataa attgcagcat cttactattc tacagcttcc 2760
ttagaaagga ggtgatccag ccgcaggttc ccctacggct accttgttac gacttcaccc 280
23
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
cagtcgctga ccctaccgtg gtcacctgcc tccttacggt tagcacagtg ccttcgggca 2980
gaaccaactc ccatggtgtg acgggcggtg tgtacaaggc ccgggaacgt attcaccgcg 2940
gcatgctgat ccgcgattac tagcgattcc aacttcatgc actcgagttg cagagtgcaa 3000
tccgaactga gatggctttt ggagattagc tcacactcgg gtgcttgctg cccactgtca 3060
ccaccattgt agcacgtgtg tagcccagcc cgtaagggcc atgaggactt gacgtcatcc 3120
ccaccttcct ccagcttatc actggcagtc cctttagagt gcccaactaa atgatggcaa 3180
ctaaaggcga gggttgcgct cgttgcggga cttaacccaa catctcacga cacgagctga 3290
cgacagccat gcagcacctg tatccggtcc agccgaactg aaagacacat ctctgtgtcc 3300
gcgaccggta tgtcaagggc tggtaaggtt ctgcgcgttg cttcgaatta aaccacatgc 3360
tccaccgctt gtgcgggccc ccgtcaattc ctttgagttt taatcttgcg accgtactcc 3420
ccaggcggaa tgtttaatgc gttagctgcg ccaccgaaga gtaaactccc cgacggctaa 3480
cattcatcgt ttacggcgtg gactaccagg gtatctaatc ctgtttgctc cccacgcttt 3540
cgcacctcag cgtcagtaat ggtccagtga gccgccttcg ccactggtgt tcctccgaat 3600
atctacgaat ttcacctcta cactcggaat tcvng*ynrm amhadatara grahntwhnm 3660
artndatnst athbcdcmbg tmsnwrmans ymbarahcbc whnmartnwh nmartnhddt 3?20
bcbwhnmart nnrmawhnma rtnmcrstwr dbbdhccdbc bcttdgdanb cdaa*rtntr 3780
ywnstamyta bbcdcddmwm wrddcmntda tncatsmmar ynrmatncdy dcmntsmmar 3890
ynrmatncmb mcrstwrddc mntmswrddc wrddcmnt 3878
<210> 20
<211> 2287
<212> DNA
<213> Stealth W rus
<400> 20
gbbsbcgaat tccgcatcca gaactacgat ataacgacta tccgcaccag ttttcgggtg 60
gtcagcgtca gcgtatcgtt attgctatcg cattggcggg gtcgcctgaa atcatcatcg 120
ccgatgagcc aacttctgct cttgacgcca ccgtacaaaa acagattctt gcactgttgc 180
ggaagctagt tgatgaaacc gaggtgtcaa ttattctggt tacccatgat atgggcgtta 240
tcgcagaaat tgccgacaaa gttctggtga tgcgccacgg cagggtcgtc gaacagaacc 300
agacgagcgc catccttgat gcaccgcaag atgactatac gcgcaaattg ttggcggcag 360
tcccaagact tcatgtttcc agtggcgagc ttcggggtaa tggggcgacg acaagcgagg 420
ggaatgaggc acaggataaa gggattaggc gctctgccga tattcttgtt gccacagata 480
tctcgaaaag ctttcgttca gggggcgcgc catggccttt agcaagtgcg gtaccgcagc 590
aagcacttaa gaatgtttcg atccgcctaa agcgcggcac aatcacaggc attgtcggtg 600
aaagtggaag cggcaaaacc actatcggcc ggatcatcgc ggggctggaa acggcaagcg 660
atggcgaggt ttcgatcagc gggaaaaaat acgacgtcac gaagaagggg cgaaccagtg 720
gcatcctcgg gcgagtgcag atgatctttc aggatccgtc cgtctcactg aacccgcgca 780
tgaccatcgg tgatgctttg aacgaagccg ttcggtcgat taacaatgtt actggacaac 840
ggacaatact cggtattggc ccgatgatgg acaggctcaa tctcgccaga agctttctca 900
cccggtaccc acatcagctc tcaggtggac agaaacaacg tgtctgcatt gcaagagcac 960
tccttgctga tccgcaaatc atcgtcgccg atgagcccac ctcagcactc gacgtctccg 1020
ttcaggcgga gattatcgaa ctactgaagg aacggattat tgaagatgat atttcgatga 1090
tcttcatctc ccacgacctc gccgtcgttc aggatatttg cagccacatc tatattttcc 1140
gaaacgggcg tatcgaagat agcggcccat cgatatcaat cttttcgcaa tcgagaaatg 1200
cttacacgcg aagcctagtc gaggcgcggt cgaagcgatt tatccagtaa gaacagtcca 1260
ccaaatccat aagggcggcc gaccggcctg ggcggaatga caccgcgcca gattgtcgga 1320
ggtcagtcgc tattccaaaa atgaggacaa tcatgaacgg tagcttcacc atcacggtaa 1330
24
CA 02282858 1999-08-24
WO 99/34019 PCT/US98I27744
ccggacagtc tctgatcaag caggatacac gtggcatttt caatcccgga tttcaggatg 1440
tctctacact aatcaaaaac acggacctgg cttttacgaa ctttgaaggc accattttgg 1500
gccgttatgg cggctggcca ctgaagggat cattttttga ctgcagcaag ccggtggttc 1560
tggatgcatt acaggatatt ggctttcgtg cgctgtcgtt gtccaacaat cacgcatttg 1620
acctggggcc gtcgggcatc ctgtccacga tcgaggaggt cgatcagcgg ggctttttgc 1680
acgccggcat tgggcgcaac caccgcgaag cggcctgccc cagccttggt caaattggtc 1740
agcgtaaagt cgctatcgtc gctatggatg gcggccctgg ccctgatttc atgtatgccg 1800
atgattcagg gattgggcgt ccggaacgcc ccggtatcaa tcggctgggt atctcccaga 1860
tcatcgatgt cgacaacgat acattccagg agcttcgttc gatacgcgac aaggttggtt 1920
atacagagct tgccctgacc aatgacagtc agcccaacga tccatatccc gtcgacgaga 1980
caaaagaggt ttgcatcgga cgggcagtat tccgtcgatc aaaagaattc vngnrmamha 2040
dataragrah ntwhnmartn datnstathb cdcmbgtmsn wrmansymba rahbcwhnma 2100
rtnwhnmart nhddtbcbwh nmartnnrma whnmartnmc rstwrddhcc dbbcttdgda 2160
nbcdaa*rtn trywyvtabw rddcmntsmm arynrmatnd cmntsmmary nrmatndath 2220
hdcmbtathb cdcddmwsta thbcdcdatn stathbcdcm crstwrddcm ntmswrddcw 2280
rddcmnt 2287
<210> 21
<211> 2568
<212> DNA
<213> Stealth virus
<400> 21
gbbnbcgaat tcaaagttaa agargggtgt ttcagcatca agccctgaag cttcaattga 60
agttttagaa agtcaaaaaa ttgctcttga atcacaattc agagctaaaa atgaacgtgt 120
aaatacaatt gctgccgaaa tcaattcaac tttagctctt aaaaatgatt atgaagctac 180
acgtcgtaaa ttaacagatg ctttctcagc taaaattggt gaaagagaaa gatcaaaaac 240
tttacttgaa caaagtagag aaagacttgc ttctcaatac aaaatgacat ttgaagcagc 300
tgaaaaagtt catcacttag aaatgaatcg tgatcaagct gaagaaattg ttcgtcaatt 360
aagagaagaa attgaaggct taggtaacgt taacttagaa gctcttgaac aattagttga 420
agaagaaaaa cgttacaatg aatatgccga aggtgaaaga gaattaagtg ctgcaaaaga 480
aacacttgaa agcgctattg cagacatgga taaaatcatt atcactcgtc taactaacat 540
tattaatgat gttaatgatg aatttaacaa tgtctttaga acaatgttcg gtggtggtac 600
tgcaaaatta tttttcagca accctaaaga tattttagaa tcaggtgttg aaatcgaagc 660
tcaacctcct ggaaaaaata ttaaaaacct taaattattc tcaggcggtg aaaaatcact 720
tatcgctatc tcattattat ttggtattct taaagctcgt ccattacctc tttgtatcct 780
tgacgaagtt gaagctgcac ttgacgaagc taatgttgtt cgttatgcag aataccttca 840
acaacttaaa gaaaaaactc aattcttggt tattacacac cgtcatggaa caatgtcaag 900
agttgacaca ttatttggtg caacaatgca aaaccgtggt gttacaagct tcttcagcat 960
tcaattagca gatgctaaaa aacttgttgc agacgaacaa aaagaagaat tagaaccttc 1020
aaacaaaaac aaataataat caaataatta ttgtgcttaa tcataggcac aatttttata 1080
tatttgccca atcaatctat aaaaaagctt tattagtaaa atccatcaat tttaaatgaa 1140
aaattgttga gaaaaatctc acaaatttaa ttattgaaaa taattataaa atattaaaat 1200
ttatattaat aaatatagcg aataatcatt tataattaga gtactaaaat tgaaaggcca 1260
agaatgagaa aatatcaacc tattcaaaat tcagcaagta tcgaaattgt tcaaaataac 130
cacgactaca aattcaatag tgtaagtagt cgtgtttatc gtgatccaaa aaatcaaata 1380
tcacctcgcg tttatcgcgt catccgtgct gaacaaatgc ttaagatttt aatcctttct 1440
atttcatttg taattatggc tgcttcaatt attctcttca cattagtcta tgctaaagtt 1500
~5
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
ggtatcttca acaaagaaca aagattaatt ggctaccttg tactttttgg atcaagtgcc 1560
tttatctcaa tggcaattgg ttttaaaaat ctgattgaaa atattcaatg atctcacaca 1620
gttcaaagat atcgtgatgc agtaagtaat ggtgattaca cttcaagtag tacttttcat 1680
attgcttatc gtaagatagt acttaaagat gttaatttaa cttgaatgct tgtttttgtc 1740
ttaacatatc taggcattat tacagcaata gtttatggac tttatatgtc aaatcgttga 1800
tattatgaaa ctgatacatt aaaaatcaat tttgaatgag ctaaatgact tgatagaggt 1860
tttggcaaca caattctatt ctgtattatt agtgttatta ttatggcttc ttcaatagcg 1920
gcgtatattt taataagatt atttgataaa aaacgtttag ctgacattag tgattttctc 1980
ggtgaacgtt ctgttgaaat tcatgaacaa gttgagcaaa gcaaaaaaga tcgtaacaaa 2040
atgtgactta gaatttatct agtagtagtt gctttaacaa ttcttttacc tcttgcttta 2100
gctctagttg ctctttgaag atttattgtt aaacgtcgta aaaaggttgt agcttaaaaa 2160
aattataagg ttttaaaaag ccttattttt tattaaataa ttctattatt tacttgtttt 2220
atatacattt tagtcaaaat tatttttatt tttttgtttt tattttcaaa tttttgctta 2280
tacaattttt atatggaggc attaaatgga aaacacaaaa agaacaaaat taactaaaac 2340
atcatgaatt cwhanrmamh adataragra hntwhnmart ndatnstath bcdcmmmbgt 2900
msnwrmansy mbarahbcwh nmartnwhnm artnhddtbc bwhnmartnn rmawhnmart 2460
nmcrstwrdd hccdbbcttd gdanbcadaa ~rtntrytab wrddcmntsm marynrmatn 250
dcmntsmmar ynrmatncmb mcrstwrddc mntmswrddc wrddcmnt 2568
<210> 22
<211> 8387
<212> DNA
<213> Stealth virus
<400> 22
rgbbcnbcga attctttctc gtgatctcgt ataaccccgg atatcaaagc gcggtcaagg 60
acctgaaaga gtccacgaag cagcggttcg ccgccttgca cttcagctat gcctccgcgg 120
accgggagcg agaaatcgtc gcggaagaag cgaaaataag cagtgagctt gcccgccaac 180
ttgttgcaat cgcaacggcg tcgcgcaacc ttgctggcaa gggcctggat gaaggcgcgt 290
cgacccgaac gttgatccgg gctgggcggt tgatcgcgca aggcataccg ccggcagatg 300
cgtgtgagct cgcgatcatc tcaccggtca cggacgacgt tgcagttcgg gacgcgctgc 360
gctccacggt aatggcatgt ctctaacctc cccgggacag gccttgcctg aagacgcaat 920
ggaatcacgg ctcatgggcc gcatggagct ttttacgtcc tacaggacta ctcggactga 480
actaggacgc gtgcatacct cgaaggaact tggcgagtgg atcgaaagca atttgcggct 540
attcgacgcc aacgccggac aaccgctttt ccagatgctc tggcgactgc aactccgcct 600
ggcgagatgt gctggcgctg ccgcattgat caaaatcgct gattcgacct atcacatgtg 660
tctttcctcc ggtgctttgg caaccacgag gtttctcgag gccgtgttga tcaggaccag 720
cttcgaagag acgggcgagg actggatctc cgcgttggcc ggaatagcta gactggcacc 780
gtgcgctcct gaaatggcag gggcgatagt gattaacctc tcgacgctgt tagagcacct 840
tgccgttgga aatatagcgg cttgggctga ggatgccttg cggctctacc ctcgcgaccg 900
gcagaagcga cttgcgtatt atcggcttga cgatccgacg gcgatagagc ggctcgctgc 960
ccatgaaggc atcgtaaggt ttgaggtgca tactggtcgg ctgacccatc tggtcaaagc 100
gctgttcaat cgggaactta aggtgcaagt cgtcccgcct catacagcaa cgtctatcca 1080
gcgaacccgg ctcgccggcg acgttattct tgtccctggt gtcccgccga acattgttcg 1140
tggcaaaggc tcggagtatt tcgaggcggc tgttttgcac ggactgtgcc accagacctt 1200
cacgccggcc cgttttcccg tcggaaagat gaagccgcta cagcttgcac tcgtctcgct 1260
gctggaagat gcccgtgtcg agcgtctcgc ggtgcgggag tggcctggca ttcaaagctt 130
ttggcttccc tttcatatgg atctcggtgt tcgagcccgc agcgccgagg ggctacttgc 1380
26
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
gcgactggcg cgtgctctag cggatccatc ccatgatgat gacgacgcct gggttcaaaa 1940
agggcggatg tttttcgaag ctgcgttcgc cgctaccccg aatgaccttc tcttctgtga 1500
gccggttggc gagggtcctc gggcatgatc tcggccagat gcggatccct ttcgacgcaa 1560
agtcttactt agtcactccg ccttacagag acgacggctt aggtctcttc caaattgacg 1620
atcccagcca atcagatgag gaaacgctcg aaatactcct cgacgcagca agaatcctgc 1680
cggatgaaga cccttccaaa cctgctgcgc cggaaggttc ggatcaatcg gcttcgataa 1740
agtttgtaga ggccgatcct gacaagggtg cgcttctggg cctctatccg gaatgggact 1800
acagactcgg gtcggaaacg aagtcggctg ttagtgtatt tgcagatcag ataacaacag 1860
tcggcagtcc gagctggctt gacgacgaac ttgcgataca tcgccgcgaa agcggcgcac 1920
tgcgcgcctt gctacgccgg tctagaacag gccgcaccgt gcgccttaag aaccgattgg 1980
atggcgacga tatcgacctc gatgctgttg tcgaaaacct ggtttcctgt cacgcgggcc 2040
acacacctga tccgcgcctg tattcggtga aacgtcgtct cgaacgcgat gtatcgatgg 2100
cgttgctggt cgatacatcg cagtccacgg cctcacggaa agacccgacg actcccagtg 2160
tcctggaaac cgcggtggtt gcgacggctc ttctaggcga ggcgctctcc gaacttaacg 2220
acccgttcgc aatcttttcg ttctgctcta atggcaaaga tgacgttcga cttggcgcgg 2280
tcaaggattt caatgagccg tttgccgggt ctgttccgcg tcttgccggt ttgcaggcta 2340
ggttctcgac gcgcttggga gccggtgttc gtcatgtcgc cacgaagttg cacgtacaga 2400
gaacaatgag aaaggtcctt atcgtcataa ccgacggcga gcccgctgac cgtgatgtcg 2460
atgatccgga atttttgacg gaggatgcac ggcacgccat tgcaggcgcc cggtcagctg 2520
gcatggatct cttttgcgta gtgattggcg atcaggcgct ccctgtcgcg tcacgaatgt 2580
tcggcaaacg aaatacgctc tcggtgtatc gcatcgagga ccttatccca cgtctatctg 2640
aattgtactt taggttgacg gtaaattagg agtcaccaaa accatgcaaa gccggttcgg 2700
ctcaagcgat catcgcgatg tcgatcggga actggcccgt acccgctcac agcttcccga 2760
agttgcggtg aatgccgatc ggatcaggga cgtggcccgg atcacgcaca ggacgcggga 2820
gacggtgatc cagcgcgatt atgcacttga gcgggcgcaa cagcagaaac tcgacatgga 2880
gcgcggtcgg tcgcgggagc cagatcgggg cttggagcgg taagtggcga gctgccgggt 2940
attctgtcag tgtcggctcg ccgccagctc tcacgggaca aatgagacgc gccgcatccg 3000
cacagcgttc ggcgctcgcg atctttccga cgatgaagca tgccggcttt gcgatgcgct 3060
tgaaaaaagc gtggtgcaaa gccctgacag cgtgggaaca cgttgagctg cacaaaagag 3120
ttgagcagtt tcagccggtt gtaattcagt tcggttggga gcatcaccgg ataatggtct 3180
ttgagcgcta tcgtcttact cgcaatcgcg ccgatatcac cgycctagat acactttcac 3240
caaatgcccg atctcaccat gcgcctgaac catcgcagcg gagcttggcg gagtgttgtc 3300
gtgacaagcg ttgttgacgg tgtttttgaa ggcagcgaac tttcccgcat gggagggatc 3360
gcgagataat agatgctcca ttctcggaga cagccattcc atggttttgc cgtcatagtc 3420
ggacagtgag gcgaccatat ctcctgaggt gtgccgatcg ctaaccaaga tttccttgca 3980
gaagcgttcg ccggcatccc gcaactggat tccgcattct ttcctcaaat caggatggcc 3540
gccacgcgct agcgattttg cacggttgag ctttgctaga agtgcgtcac tggtgttctc 3600
gatgatggtc cccttcccgg ctgtctctat gaacagctgt gctgtcgaga caccgaggtg 3660
acgataccga atttccaact cttcccaggt tccatggtcc tgtgtcagta caatcacctg 3720
gatcggcaag ttgagcagtg ccgaaagcac ccccgcattg aaatgaccgc gatagtcctc 3780
atcacttgaa agcacagggt catccagaat gatgaaaccg accccttcat gttccgcgcg 3840
agcaagaaac agcgccagtc ccaggcagtg aagttgtgac tggctgaaaa ttgcaatgac 3900
gtcgcgcagt tttgcggcct ctctgtctgt cgtggcagtc aagccggcct tgaaatcgat 3960
tgtcctcttc gcgcctttcc gaggctgaac agcagagaag aaagtcggct catccggccg 4020
gagaagctcc caccaggcct ggatagcttc gctatattca gagaactttt cttcgagcac 4080
cttttctttt gctgcatcga cctgctttag ggccgtctcc agctcctttg ataccgtcgt 4140
gaccgccctt cgttcaacga gtgcgctacg aagtcctctc ggatctgcag cgagttctag 9200
aagatcctgc catcccgtag tgtccgactt cgcatccaaa atagaggtga gcgcttggcg 4260
27
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/Z7744
taaggtctga gctgcggcgt cgtaagcctc cagggcgtct gagaaggatt ttcgtagcct 4320
agccacctct tggaagtcca ccttcagctt ttccttttca atttcggcag cacttatgtc 4380
gtcaacatgc ttttccaaca gcaccttgag cgctgaagcc cgctgcctaa gtttcgacga 9440
gatgaggaga accggacgga cggccacaag ccacggccca acaactgcat cggctccgtc 4500
cccaagtagt tcgtgcaaac gagcaactgt gaaaccggca tcccgtcgct tcctgccagg 9560
ggttttgaaa aattcaggca aagccgcctt ggcagcatca gccaggctat cagcgctcgt 4620
cataagccgg cctaaggccg cctttgcatt ggcctctgca gttttgaaat cttttgttgc 4680
agcaacgtgc tgccgtaaaa gttcaacccg tgcaggcgtc agggcatctt cgacgccaca 4740
caacgggcag tccacctgct cggttgtttc ggctatatca ggcaatttga gcgcctcgac 4800
aaaaagcgcg gcaagctgcc gcgtttcttc gtctaccttc gccttttcgc cggtataaag 9860
ctcgatttgg gaccagttct cgtcgtccgg acaactccat ccggccagtg cggatcgctc 4920
gaagttccgg attggaaaag ttttactacg gagctcagtg agtagctcgt tcagggccga 9980
ataccgctcc tcagaagtgg ccggtatggt ctggttcgca tcttcgagca gtaatcgcac 5040
acattcatca agctgctccc taatctgagc tgcttcggga agtttgcttt cgaccttcga 5100
taaaactggc tgcatgagcc ggtgggcggc acaggaatcg aactgcgcaa gggctggatc 5160
gtcaggctgc cgaaagtctg cctctaggcc cgcaatcatg ttccggagtt catccagatc 5220
agtcacttca aaaagtgctt tgaagtaagt ggcgcgatcc tggggcttta ctgaaaaaat 5280
gtagctgagg gtgtgttgtg ccagtaccgg tgcttgaaga ggcggctgag ataggacgat 5340
accaagggcg acaagatcag actcttgtgc cggcgcacca tcaatctcta gtcgcgaagc 5900
gcagttctga cgtttggcgt agtctgctgt cagaactcgc ttaacaacgt gttctgtgcc 5460
gtcgggagct acgatcctcg ccgccacata gacctcgtga ttcactggca aatgagcgtt 5520
gcgaagagcg tctgcaaact cgtcttgact gctcgccatc atctcacgcc gtgagatgca 5580
gccggtcaaa agaaattcaa aagcctcccc taggctgctc ttccccttgc tgtttggtcc 5640
ccacacaacg gcgagatcac tggggagact caacgtctgc tctgtaccgc catatgcacg 5700
aaagcctttg aggctgagtg acctaattct tgctaccaag gtcctgcctc acttgttcga 5760
gcctttcggt crcaatgcgt ttcaacgcgt cgcgatcacc cctggaatca aggtgtgctt 5820
gaaccaggag cgaagacaaa gtctccggct traggtgctt ttgtaggcgt tcgctattac 5880
tctctggctc cagagcagcc tcgctatttt gcatgtgtta ccccccatag catggtgcct 5940
gcttcgttcg attttgcaag tttattgcgc cttcgcacca ttcaaaatgg accgattgtt 6000
ggacatcaac accgagagga taaaagtgct ccaaggatat atcgttcgcg tccaacaaat 6060
acgtctacta ttctattgcc yaataatcgg tattgaatca gaatctggac atgctcatcg 6120
gttacgcgcg cgtctcaacc acagatcaga acctcgacct ccagcgggat gcgcttcaac 6180
gcgccggctg ccagaagatt ttcgaagaga agaaatccgg cagggccggc accaagcggc 6290
aggagttcga tgccgctctt gcctacctgc gcgctgaaga cgttctggta gtgtggaagc 6300
tagaccgact gggtcgatcg ctcgtcgaga tgatgcgcac gattgatggc ctgcagaaga 6360
acggcgtcat gtttcaaagc ctgaccgagc acttcgatag cgagactgcc catggccgtt 690
tcgctctcca gatgcacggc gccatggcgg aatacttcct cgatctcaat cgagaacgca 6480
ccatggaagg cctgaaagcc gccttggcgc gcgggaagaa aggtgggcga ccgcgcaagc 6540
tatcggagrc cgaccttgaa gcaggcaagg cgatgctggt cgccggcact attcctgttg 6600
cgcagatcgc caagcggctg ggcctcagcc gggccggatt ctacaactac tttccgcaag 6660
cccgtgcaac agccttggtc aaggaggatc gttgatgccg atccgtaaaa ctctctcata 6720
tctctgtaaa gccggatgca acgatgctga aaactgacac ccgccaagcg aattggcgtc 6780
gtgccaatcg atcggcctgg aagccgagca ggacttgata tctgatcttg cgtccagtct 6890
ggccgcgacc ggaaccagct ctcgaaaaca aacctgaatt tggaaagaac cgatcgacgt 6900
ttcccaccat tatgccacgt attgcgatag catcagcggt aaccgaagcc catcacgtag 6960
tcgcgcatta acgcctcttc tgtcgtggac tccttgagca gcgcctgcag tatatccctg 7020
gcgttgagca cgcccaacgg acgggactcc tcgtcaacaa atgggatgtt tttcaggctt 7080
ctttcattca tgcggtgcca tagatcctcc agcagatctc ctgactgaca aagcatgaca 7190
~8
CA 02282858 1999-08-24
WO 99/34019 PCf/US98/27744
tcttgcgtca tcgcaatgga cgacgatgcc aggcaacctg ccccctggca ctggctgatc 7200
tgagcgacga catcggtctt ggtgataacg cctcgcagga tgccagtggc gctacaaacg 7260
agcaaaatat cggttcctga cccaagaagc cgcgcagcct cgattagatg cgcatcatca 7320
gcgatagtga caagccgttc acgcgcttcc ggtaacaaac tctcaacaaa catcacctgt 7380
cccatccaaa atgcaacccc acggacccac agccatagcc tatcacaagt gtgagtaagg 7440
tgtaatgctg tgaacagaca atatttagcc acgataaagc ggacgcaccc acgaacgcag 7500
cagccatcgt ggtcgtggaa tggatgtatt cctcgatcac aattctgggc caagatgctg 7560
gtaaccggac acccaggcca gcgggtaaag ctaatattcg aggcgaaatc actacactat 7620
tctcgtatat cactttcggc tggataaatt aaaccttccc cattcatgac agctccaggc 7680
gtcatgctgg cctcattgac ttgcgatgac cccaggatgt gcatcacgct ttcgccttgg 7790
ctgatcaggt agtccgtgat gatccgccga tgacagcgcc accatacagc ctctgcacac 7800
atgattgcgc agcggtgttt gtttcctagc gccctgagtt gggcaagtcc gtcggcaaac 7860
ggcgcactca acgcatagtc tgcatagtta cggaagctgc gtacgcgcca aaacccgttc 7920
ggcgactgct ccaaattccg cgtcttacct cgaagcccgc caagtgtcgc aatatgttga 7980
tagccaattt gccaaggcgc caacgttgcg gggaggcaat cgccgttgaa ctgcggatta 8040
gtgcgcgaac gcggcattat tctcacatca acgacgaaat caacgcggga ctctcggagc 8100
agatcgacga attcwha*yw vtsrnmkhg* ***dcbanrm amhadatara grahnt*whn 8160
martndatns tathbcdcmv vbgtmsnwrm ansymbarah bcwhnmartn whnmartnhd 8220
dtbcbwhnma rtnnrmawhn martnmcrst wrddhccdbb cttdgdanbc bdaa*abcdh 8280
kmnrtntrya stabwrddcm ntsmmarynr matndcmnts mmarynrmat nwgcmbkttr 8340
sadmnstrat rdskbwwcwm crstwrddcm ntmswrddcw rddcmnt 8387
<210> 23
<211> 6088
<212> DNA
<213> Stealth virus
<900> 23
cbgbbrvgnv vvvkvbcgaa ttcaaagact tgaccgtctt ggatgacggc aagcgaggaa 60
acttgagaga ctggctaagg aaaaaatatg agcactggcg ctacggaccc tccggagggt 120
ctaacagagt tgagtattat tcgccacccg acgaacgcgc cggcgagacc agagaggaga 180
tggttactat ccagccgccg cctcccaaac aaactgtggt gactatagag ggcggacaga 240
ctgtgaccaa aatctacaaa gggcaacctg actcaactga gcagtgcgag cggccgagcg 300
tagctgaacc gctgatgatc gttcaacatg aacttgaatg cgccatcaca atggacggtg 360
atgaggcctc ctgagctatt gtgtgcgggc aggcggacgt gggacggacc accgtgacgc 920
agcttcagag actaataagt tttcaccgtt ccccgcctgc gctgcctgca gctaaaaggc 480
ctgtgagctg gacgctcaga actatggacc tggccgtgct agtggccacc gtgttggcga 590
ttatcattct gttgatgatc gttatttcta tctgctgcgc taaaccttgg cggagcccga 600
actcgcgcta cttcaaccct ccgtttctgg tgtacagcaw gagatccgcg agaggggcgg 660
acgaggactt ggagccctgc ttcgaggaca ctgtgctgat tcttgaggct atgagcccgc 720
agcccgtccc gcagtaaacc ctcaccatgc gcgccgtgcg gttcagaaaa ggtccgagag 78:)
aagacggagc ggtcgatgaa accgcgctgc tggtgaccga gtgggagtct ccggaccacc 840
cctcggacgc ggattcggcc ctggaacaga ctattgagga cgagcgagcc agactcgtgt 900
cctccgtgcc ggtgccggct c~gcgagccg cgatgttttt gcgacgcgcc acggtggcct 960
tgaccgtcct gttggtggct ctaacgccgc gggtgaaggc ggacatcgat tacctgatgt 100
gggacgagtg ctacgacagc ggctctccgg caccgctcat tatgccgctg ggatcccaca 1080
tcacggtgcc ctgcaccttt ttgcctcact cgtggccgat gatttccatc cgcgctcggt 1140
tctgtcaatc cgagtatgcg ggtcacgaac tggtggtgaa cgtcaccaac ggaacgctag 1200
29
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
acactgatgg actgacccct cttttgcaca atgctagctg gaaatttgta gacatgactc 1260
ttggacattc tgtaatgctg tttttcaata taactgataa caccactggc atgtttgatt 1320
gtttgttgcg caacgagact cacggttaca tgaccacgcg gtttacggtc attacacaga 1380
tagagacttt gcacagacca ggggagcgtg agtgtgtgcc taagttggga tttaaatccg 1440
atggtgataa gatttggacc actgaacaca atgagtggca gcgccataac tgtgggactt 1500
tctacggctt tgacaggctg tactactatt tggtcgctac taacgagtcc aacaccaaac 1560
cgccttgccc cccgaacgaa cccgatcgtt gttggcccgt cgtgcagcgg tatactttgg 1620
acggggactg ctaccgcatc caggctcctc gacgccgcaa gttgcgtcct tactctaatc 1680
atgagggcgg acacggacta cggtttacgg atgtgccctg gttgaccctg ggaatgactg 1740
tgatgttcat aggaggtgtg tgcatggggc tggtggtggt ggttcgcctg gcgtgcggcg 1800
agtgttgccg caactacgag cgctttaaaa agaagagacg cggctaccga cccctgtctg 1860
gacagtttat gcgtgcgccc gactacgacg agctgtaccc cagcgaggag gcgttcagca 1920
agtcatacga ggagctgttc aatactcaag ctaatgatac ctatccagaa ccccccttgt 1980
atagtgaagt tcagttcccc ttgtatagtg aaataaagag acgcttgtaa gctttcacaa 2040
ttggcgcgtt tatgattgtg ttctgtgcgt gtgtggcgtg ttggaagcgt ckggtgccgg 2100
agggtaagat ggcggattgg ggcacgtgta tttacctgac ggtgttcggt tcgtaaaccg 2160
ctggcccgtc aacaacaccg cgcaataggg tcagtcaggg gacggcggcg cgggtccgag 2220
aaccatgagc caacccagag gaatatgctg ctactgccgg tcgtctggac cgttgtcgtg 2280
gcaagtgggt ccgccgcatc cccgtgtaag ccgaatgagt acgcggtggg ttcggagtgc 2340
tgcccgaagt gcggtaacgc aggctacagg gtaagaacga actgtagcga atccaccggg 2900
acggtctgcg agccctgtcc gccgggatca tacaataaca acaccgacag gattaactgc 2460
accgcgtgtg acatatgcaa cgcctcgtcc gtagcggtga aaaattgcac cgccacccag 250
aacgcaagat gccggccgat caacagtact gttacgcact tagatgccag accgagtcac 2580
cacggcggca accactcgtg ggaatcggac tacgactcga ctcgggactg gtggttcata 2690
ctggtgtttg tggtgtttct gttttccgtg atcctactga tcctgggctg cagactgatt 2700
ctgttacaca ccacgtacgg caagatgctg acggcttaca tgtatgaaag gattacgtga 2760
gatgttgtga actgttgtga gatgtgatga atgttagata atggcataac ccagatgtcc 2820
gtgtccccgt ttgatcaact ccaccatacg tgttttatta gcctaacctg ttcacgcaac 2880
cacattgcac ataataaaac aatctcagtc acgatgcgag tctgatatgt ttattggtat 2940
ttgtacctac ctgcgcgatt tcccctgagc actttagtat cggacacgtg acgagcggcg 3000
acgaatccgg gcgtacggtg acggaatatt tccgtctgat gggctttata agtccgattg 3060
taaatcgcat cggtccccct cgaaaacatc atggtctttt atcagtaccg caacgccgtg 310
cagttactgt ccgcgcgacc tcgcgacggg ccgggacgct gggagcgctt gacacaccac 3180
gcggcctacg ccgccgacca cggggcctgc accgtactga tggctacctc acagagactc 3290
tccctcgtcc tccggaggca tagcgccata tctgctgtca ccctacgcct tatccctgct 3300
aaaatcctga agaaacttga agaatcggaa tggattccgg gcgcctggat cgcttcagag 3360
acgttcccta cttcggacgt tatcatctga taacaatgca catgcatact atgggacacg 3920
aatactggac actgtccgag ctgctaattt gtctatgaag aagaccaatt gcgcttaatc 3480
aatttccgtt actgtgaacg ccattatgcg gcctgttgca ctactgatcc gtcttctgtg 3540
ttgctgctac ttactttcgg tactaccctt gactggccgc ccgttatcct aaacgccgtt 3600
atgcggcgtt tggtactgat ttgttttttg tgttgctgct acttatgcac ggtacgaccc 3660
gccactacac gacaagaaca ctgtccttgc gggaatacga agccattaaa ctttatacct 370
ccgaaagcgg attgtctatg gattcatcgt tctgatggac cttgcggtaa cgaagttaca 3780
gcccactttc cacccacagt aacaaagaca aatggaaaac cgcggaaacc actgtgcttg 3840
aactacacat atgttgacaa tgtcgttaaa aacgtaactg acgatggaac ttattgcata 3900
cataaaaacg ttactaaatg gctactaacg acatgtacca actgcacacc aacaactttg 3960
taccaaagag ttagcgatat tcgggaaaaa gaatggtggt tgtggcagcg aatcccaaac 400
ttgtggaggt agggtaaaat gtaaagcaat acaaatatga ttttttaagg cagcttcatt 4080
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
aagtaaagat taatcggtaa ttgaaccgtt atgtgtatcc gtgcagtatg tatttttcta 4140
tgtatcatcc tgttaggtac gtacagtgtt ggaactaaag agcatcggtg taattgtatc 4200
gggagttata ataaacgacc tctaccaaga ggaatacaat gtgtttggat taactatccc 4260
agtgcagcat gtgacaaaat tgaagctata gcatatttca attatacggt tagaaaaaca 9320
cctgtctgct tacattacca aacctatcaa cgtaggcttc ccccatcccc tggagcctgg 4380
tgttggctta acaaaaccca cgtagtaaaa gtacacgact gggactgtaa atggtgccac 4940
cgttttgaac cttacatggg cgtgtctcat tgatagtaca cccagataat tgaaaatgct 9500
aatatacatt gatgctccga acactcaaca gctcacggtt attcttgtga aaatcaaaca 4560
acatatcaag gtaaaacaac cgccatgaat gtaatgtgga gtcctcggtt tctggctgta 4620
gctctactga ttgttagttt gattgcatac agcgaatcct cgcaaggaat acgttgtgag 4680
tgtaaaaaag gtacacaaaa gattcctgaa aataaaatcg ttgtaaagaa aatgaagaga 4740
ccatcaggac ctaatcaccc ccgtacagaa gttaaagatt ccacaaaaca accaggtaga 4800
gatccaatgg gacgaccagt ctccatatag caccctaaga aaaattgaag atgtttatct 4860
acacacaatc ctcaaacgag ccagaactca cgtttattgt cgtacgaaga aaacaacaaa 4920
ctaacaaaaa gaaaccgcca tgaaagctct atacaatccc cggtttctcg gtgtgaccct 4980
actattgatg agtctgattg cttactgcca atccacaacc gaactgcgtt gccagtgcac 5040
acaaaccgtg caagggattc atccaaagaa catccaaagc gtgagcatca aagacaaagg 5100
acctaactgc cccaaccagg aagttatagc tacactgaag aacggacaaa aagtctgctt 5160
gaatcccaca gcacctatgg tgcaaaaaat tttaaagaag acgataacag ataattaaac 5220
ttgctttacg ttttgataga tcggcaataa accagttggg aacgtttaca ccgctttaca 5280
atagatgtga aaataccaat cgtgcaacag accgctctta ccggatgaat ctgcaacgtt 5390
tcctgagcta ccatgaaaac aagccaagag ccaaacatgt caatcatcga atcgctttgg 5400
aagttgctca gagcaacggt tagtttattc atagaaactt acatcgttac aaaagcaaac 5960
cgtaatgcaa tattctctat cacacttgtt ggtggcgacc ctgttgggta cgctactagc 5520
atccactatg gtgtttgctg ataaagaaga acgttgtctt tgccccaaaa ccatacaagg 5580
gattcatccg aaaaacattc aatctgttga actgcatgaa ccaagagaca tgtgtcctaa 5690
cgttgaagtc atgtaagttt gttggtattg cgttatcatc ggtaaattgg cgcatgagat 5700
aacttacaat tccttatact tttcctattt acacagcgcc aaactgaaaa acggaaatga 5760
agtttgcctt aacacagagg gtcccatggt taagaagatt attgaaaaaa tgagagatcg 5820
tgaaattgaa agaattcwha *ywvtsrnmn rmamhadata ragrahntrw hnmartndat 5880
nstathbcdc mbgtmsnwrm ansymbarah bcwhnmartn whnmartnhd dtbcbwhnma 5940
rtnnrmawhn martnmcrst wrdmmdhccd bbcttdgdan bcdaaadrtn trytab*wrd 6000
dcmntrsmma rynrmatndc mntsmmaryn rmatnbcmbc cbccbbbbbb bbbbbbbatc 6060
mcrstwrddc mntmswrddc wrddcmnt 6088
<210> 24
<211> 5059
<212> DNA
<213> Stealth W rus
<400> 29
tvsgbbtnnn nnnnbbbbbn bvwvvvvvn vvvwnnvvv vnvnvbbnnn nvrnnvbbbs 60
tathadatat nanarcangr nmnkysmanc ytmgavrsam arnctnthca rmmnsystms 120
trcgnandrs ndtvrsnctn sasccssmmn rsnscanrad catrgnvrss bydstr,~ngn 180
ctdcsrrtth rasrgnyvrs ssymtmsana ctvrsnctnm ayccrdrngt htmrdrrdtg 29n
nratarmary carmmnrsns andcanasba byrdctcarm mndamagnct dnvranctdc 300
snsaysvrnc tnscanccrt hmmnsystms mardramasa rstmmatrty chmthraycn 36.)
cdntnctnwt hhmanmmndc ncyvrshvrs ccgntcdcts nmmncmtncc rtanvrssma 42~)
31
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
yasntrrwth mmngcadnss thrghschmc hansmsasdw nrgatnthrs snhstcmatb 480
tyantgnsnd ctnmmnsrss vcytknsand ratdvrknsa ndbyrmanng nactvascan 540
ccrnatntnc tnsstathad atatnwasrs dasadstnct rcsswhrbya vrscdrmana 600
ctvycytath cnthabsnca naccmanyng nammatryca rmmnrsnsba sdnasrshst 660
gcandngsan dnzatdsatn satycaystr ctrdcytath cvrsstwass ggstdthatt 720
hsvrssackd crtcagnsnc dngctvtarg tsrthcarmm nsystmsncs tdsnarttys 780
tathadatdv rshasrvddd atacnsstnt wththshyth ssthrstsrs ntdnthsarc 840
nrmthdrvat nthsvrsrma narcangrnm nkysmancyt mgavrsscmv thdatadntt 900
yaarntgntc dtnswthnth vrsncdngth rgnthatncd thmarmmngn ctargtrhma 960
nantcytmga vrscarmmnt ythvrshasa sacrdaddtn asncsnratd tthscnvntn 1020
ahmanandan macytmgavr ssmatrasan dmthdsrsts atastartas ncnghasbnb 1080
tandnvrcns rmthvrsrma nythcnsths ncngmrycmr saratvyshr tradtrmtht 1140
andtrmtrst sthbscrtas mdrsctdcns cmtsncngha sbnbtandsv rathcnscnt 1200
andsncstha tcdbstatst cayagndbyb astnanayss tatastsmrt nthrtncdng 1260
rgnsthhman cytmgavrsh cmvgnmthba strgramwhc hsbasdnthd dcdamnacds 1320
ncscddbyan ctdsncdntd manyaddtna cnswthsgnc antartasnc hmgytvarsh 1380
cmvrtnsths rgramdsntr rthddcdrtn tbcddbyasn gnradngram andcantrat 1440
varstysnsr tsanddtnst hatcdrcdtr anscrtnanc tnamrnamca nvrandcatn 1500
thhcmvrtns rwhchatast smrtnscdba gndwthasnc cntandnnrm rthstathvr 1560
scnssshwnn tabthhcmvr tnswhchmat chdtvrmrth stathvrscn sarndcatdb 1620
yndrnngthm atchngrgns thhcmvgnmr whchnctdan damnacdsnc dataaravaa 1680
brrhsscytm gavrsrhcmv wrachcmard tthcrrsndn gstathvrss ncthsanays 1740
sshwdasgnc antyhghrba stnandbast hmgythstat hvrssncstr hcmvcmardt 1800
hcmvrsmthm atchngsncs anaddtnacm arsncdbmad wththgnban kntrsrscmv 1860
nthscassan vngratrhmg ywassnwths cmvthanrrh cmvstratvs tathvrssnc 1920
snwhchcmar snscdbmadw thcrrsndng sncsnhcmvr hcmvandrsc mvarshwnnt 1980
abthmatchn gthstathvr ssncstthhc mvandwhnav aabtthrhcm vandscmvgn 2040
mscmmnyshw dasmarstat hvrscnthan thcrrsndng rgnccrrngw thnthhcmvg 2100
nmanamsrvd dbystathvr scnbbastan ayssthscns hwsamnacds ncscrrsndn 2160
gtthandrtn shcmvthscn cmrssnynct dscmardtnc tdsthcrrsn dngcdngrgn 2220
hcmvsmthst athvrscnsc ntandsmasg mntswhataa rdtbnsrtds ncsthatcar 2280
ydstngshdt hstathvrsr mthcrrsndn ghcmvrhcmv rscmvgnman amsrvddwth 2340
cnnthscasa ndnsvrathr amsthnsrtd sncswdbctd tdsrtthrad trmasngnra 2400
dngrammtvr mnrdrncsan dccasnamar sncdrncswr rsntbtwndr ntcnsthatc 2460
arymatchdt smarrgnsth hcmvgnmams arshwndscs snthgnmthy sncdadstra 2520
nhcmvcmrss nctdsbasar sandtntayc dsratastrt nsrshcncas atshcmvcnt 2580
ansmaddtna rtncdngsnc sntrsntnth abratryada tdadstranm tdsncsarav 2690
aabnthcytm gavrssthrs csvrathrsa gnracnsrva tnsncsthsv rssawngrcm 2700
aranstbmad wthhcmvsnc cmarsnsbtw nthstathvr sandthshcm vrhcmvands 2760
cmvsrtrrar gmntsrthdr vatnthstat hvrsrmscmv thnctdandr tnmatchngr 2820
gnsthstath vrsardstrb tdthrghtmc hthhcmvgnm thmatchngs ncswrntnrm 2880
aydstrbtdt hrghthhcmv gnmramcnsw rndthatmat chdtthrgna scanbsnrmt 2940
absmrtncdn grgnshcmvw rntrrsntdb yanythcnsr mwhchsncda tahavsarbn 3000
btandnartc arthrwasnh mgydntdwth thwrmatrrt nwhchsthma rtargtrcyt 3060
tctcmdatdm mntyaganst hcmvthsndn gscnsstntw ththndryng assmtncncr 3120
nnggndtnas amansrstat hadatdvrss tbyasscarm mndnsmchan smsathghnt 3180
sccaydtrmn dnthsstdyt haggrgatng thsthcndst athvradnas ncsthatmat 3240
chtnnvrang rgnsthhcmv gnmrbabycd skbsncthst athvrsdnam gratsnagar 3300
32
CA 02282858 1999-08-24
WO 99/34019 PCTNS98/27744
sgswthasny armatykbas tsassmdtha tthgnmcnss tsmtragmnt srathrthan 3300
asanntrngt hcytmgavra gnmtabhcmv rtnsdntdby hmgysarchn gsngsncsnt 3420
hdnatractd rmctrsstat hvrsssssss sssssthdsg natnrrstrt nsncddbyth 3980
nngrgnhcmv srrstthnsh rtrgnmstth sncswrbtan drmthadstr anhcmvanda 3540
rntrsntnth adstranbta rrsntnthtd stranhcmvh cmvrtnstat hvrscnswth 3600
hrngy*btbt* btbt*btbtb tbtbtbtct* *btbtbt*ct **btbtctct btctCt*c*b 3660
tbtcbtbtbt btbtbtbtbt *btbtbtbtb tctctct*ct ct*btbt*bt bt*btbtct* 3720
btbtctctct c**ctctct* btbtbt*ct* *btbtbtbtb tbtct*ctct btctctb*ct 3780
ctctctbbtb b*ctbbtc** btbtctctct c**ctct**b tbt*bt*btb tbtbtbtbtb 3840
*btbtctbtC tb*btb*bt* bt*ctctctc tctct*ctct ctct**btbt btbtbtbb*c 3900
tctctbtb*b tbtbtbtctc **ct*ct'ct ctct*ctct* *ctbtctctc t*bt*btbtc 3960
t*bt*ctctc tct*ctctct ctctct*ct* *btbtbtsss ssssssssss sssss*ctct 4020
ctsss*ctct s*ctbtbtbt s*ctctbtbt btbtbts*bt btctcts*bt bts*btbtbt 4080
btbtbts*bt s*btbtbtbt btbtbtbtbt ctcts*btbt btbtscttab cmarsnthst 4140
athvrssnch mgswthcytm gavrsshman andrmatrgn shmgytcytm gavrssdrnt 4200
scsstathvr scnbastnba strgngnmhc mvrhcmvscm vhcmvrhcmv scmvbtnsbt 4260
snsbtmnsns ccabcdcabc abghnvghnd bbabghnvgh nbbcdvbgba gnbcdbbstv 4320
bbcktbbghn tbabchbvwk rbrwyyhb** ********** *w******** b***'*'*** 4380
********** *******db* ******cdbc dkmstcdkms tbbbdbkrwy gmnstbghnb 4940
ntghmvwybd chmsbbydbd bdbdbdbdbn rmamhhadng dadataragr ahntsbdytt 9500
ndntdttdct r**cn*dngv *sgv***cbm rwhnmartna stathsncsd cwhnmartna 9560
stathsncsd cwhnmartna stathsncsd cwhnmartna stathsncsd cwhnmartna 460
stathsncsd cwhnmartnd atnstathbt dcwhnmartn datnstathb tdcwhnmart 4680
ndatnstath btdcwhnmar tndatnstat hbtdcwhnma rtndatnsta thbcdcbgtm 4740
snwrmansym barahdstat hadatatnan arcangrnmn kysmancytm gavrswhnma 4800
rtnwhnmart nhhtstatha datatnanar cangrnmnky smancytmga vrsmtawhnm 4860
artnnrmawh nmartnmcrs twrdnndthc cdstathada tatnanarca ngrnmnkysm 490
ancytmgavr sttdgdancd dda*abdghm nrrtntrygw nstarwtabb cdcddmwwvw 4980
rddcmntdat cdctsmmary nrmatndccd cmntsmmary nrmatnkcmb dmcrstwrdd 5040
cmntmswrdd cwrddcmnt 5059
<210> 25
<211> 2275
<212> DNA
<213> Stealth virus
<400> 25
gbbnbcgaat tctatattat ttagtaaagc atctttgaat tgttgagttc ataaccataa 60
attttcttta aagcaggata aattatgttg gcatagccta aaccttgaaa gttagcatag 12~
ttaaagcctg attgaagaaa ataacttctt aaagcaacaa taatgtaagt tcaaattgaa 180
agctttttag tttgagcttg attaacttgc acaaaatctt tgttattaga ttccatcttg 240
ttgacctccc ttgttatttt cattattact gcttgtgtta cttatgtttc gagctactcc 300
agctgcttct ttaatacctg ctagtttttt tattgatatt atgatcaaga caaaggccat 360
ggcagtaaga gcaagagcta atactgagaa tgcttgacct gtaatttttg aaataacttc 420
aaataccaga gctaaaaagt aacctaataa agcaaaacca atatattctt ttttgagcat 980
aacttttaat attaaagcaa aacctaaagc aggaagcata ccaccagcaa ctcttaatcc 540
agttcttaat caatctggaa tactgcttga gaatctagct atcccattag ctgaaacacc 600
aactaataaa ccaaatccaa atgtaacaat Cattaagact aaaatagtta catgagatag 66.7
~3
*rB
CA 02282858 1999-08-24
WO 99/34019 PCT~S9~~~~
gaatttaaac attttaaatt tgccttttgt aatttgtttt ttagccattt cacttnatcg 720
gtgacattaa tgtgaataat aatgtagtta ataattgcat taatattcct actggaattg 780
aatatccaat ataaatacct gcatccccaa ttgaaatagg ttgtgtgctt ccatgttttt 840
caacaattgc aacaactgtg gcaaaaatac ctggtgcaat tggmntccgg cggtctaaca 900
ccaccttgtg aaataccaaa gcctaatcaa acagtttgac cagcagctcc aacaataaca 960
gcggtttgaa tatcccctaa aattattcca acacctaaag cataaactat tggtgttgct 1020
gtataggtcc ccatcantag tacctgttat tgctaccgcg gctcaaactc cgataaagat 1080
agcttgaata attgaaattt ccattttgtc ctacctaact aattaattta ttttggtcaa 1140
ctaaaccttt agttacacca ggaaggcttg cagtattaaa cttaattcct aaatcaatca 1200
tttctttaat ttttgctttt tcatctttac ttagattaac tgaaggtgta attcttanca 1260
cgnatcttct cttgtatgaa cattaccaat atttatttct tcaattggta attttcctaa 1320
agctaattta taaacatcat cgnatacttt taacaacaat gtaaattaat tgtcaatcag 1380
cagctttagg tcaaatttct attaatttat caactgaata aaagctacat ctaacccctt 1940
ctggtacagt aactttcatt aattgttgtt gagtttccga aactgctgct tcatcgttag 1500
caacaataac tgagtttgat ccatttactt gcattcaaat agatgcttgt ccatgcatca 1560
atctttcatc aactctacat tgaacaattt ttgccataaa atctcccttt tatcaataag 160
gatttcaatc ctttttatat agtctcatta gtgcttcaaa gtaataataa tcacctcaaa 1680
tatttccttc atcaacacct ttttttgaat gtcatgaata aactccatgc aataaaattg 1740
gtgttccagg ttcaattttt ttattgtgat atttattaat taaatttctt aaaattaaat 1800
gagctgattt ttcgtataaa tctgttttat agtctttttg agtaatttta agcatttcta 1860
aaataccaca aactgctata gcactagctg atgagtcgcg tgattgatct gccttttcat 1920
taaaaattaa atctcagtaa caaacataat catcttgagg caaattattt aaaaattgat 1980
ttaacacttt ttgataaatt tgataagcgt ttttatctat ttttgaatta ttttttgcat 2040
attttaatgt aagtgwhanr mamhadatar agrahntwhn martndatns tathbcdcrz 2100
gtmsnwrman symbarahdd cbcwhnmart nwhnmartnh ddtbcbwhnm artnnrmawh 2160
nmartnmcrs twrdcdhccd bbcttdgdan abdaa*rtnt ry*atabwrd dcmntsmmar 2220
ynrmatndcm .ntsmmarynr matncmbmcr stwrddcmnt mswrddcwrd dcmnt 2275
<210> 26
<211> 1590
<212> DNA
<213> Stealth m rus
<400> 26
gbbmnbcgaa ttcggccgtg tatatttcaa gcaacacggc catcgccaaa gtcgtgttca 60
ctacctgtcg ttttgcctat ctcttggtga acagccatcc cataggccag ctcttggttc 120
ccccaatccc agaaaccggt tttacacaca ctcccgaaca ccacatttta caacaactgc 180
tgtcgccaga ataaaccacg ccaaacacac ataagtatgt aattgtcttt tttattgagg 290
ggtggtggaa gcggggtttt ttaaatggca gcgtgcgtcg tagatgacct ctttcgctta 300
ggcttcgcgg gagccgctgg aggagctcgg acctgttctt cgatagcagg caactcatta 360
tcaggaacat gagggatcat tgacaacacc tcatcctcca aaacgtcccc attggccgcc 420
acctcatcca cagcagtggc accagccgcg tccaaaattg aggtgctttg atcgcaatcc 980
atgtccacca aacccataac tttctgaact tcacacaggg ccacttggtc cgtagaaaac 540
ttattcagca acacctccag agtgtcgtcc tcagacatgg caaactcgcc caccaccagt 600
ttcaagatca taacgtccag agcctgcata atccgctgcg acttctgatt ctccacctcg 6E7
gcggcggggc gcgtgtgcgg ctggcaatta tccgacaaga agtcctgcag cagacgacat 72)
ttcatctggc actgccgata cagagggatc agcttgagca gatgcttcgt cacttcctga 7E:~
tccttcgcaa aagtcttaag atcctcgggc gtgatcccta acgtgctgaa gttttcctcg 89~
34
CA 02282858 1999-08-24
WO 99/34019 PCT/US98I27744
aagaagcagt gcatctcctg catgttcata tcctcgctag gctgcaacag cacatagtcc 900
gcactctgcg agactcgacg ctgacaggtg aaaactccac ataggcgccg tgccaggtcc 960
atcctccacc ggcaatgacg ctagttctgt tcgcgacaga gtatgattct gctcatatag 1020
tcgccaacgt actgtccaag tctgcatccg agcactgtgt gtttccctta ctggtgaaac 1080
accacgcctc caacctcatc tacttctgtt tgcagaccca aaaatgcacg gattcgcagc 1140
gcgtctctcc ggtattcgtc gtcaacaacg acgttttgaa tctcgcccac tacttgcaca 1200
cccgacagcc cattccgctg tcggccctgg tggacagcct caacgaagac gaaacgcggc 1260
ccatctacaa ccacttattc cgcaccgtta tctctcccga gcacggcggg gaggtgcgcg 1320
aattcwhanr mamhadatar agrahntwhn martndatns tathbcdchh gtmsnwrman 1380
symbarahdb cwhnmartnw hnmartnhdd tbcbwhnmar tnnrmawhnm artnmcrstw 1940
rddhccdbbc ttdgdanabd aartntry"t abwrddcmnt smmarynrma tndcmntsmm 1500
arynrmatnc mbmcrstwrd dcmntmswrd dcwrddcmnt 1540
<210> 27
<211> 1075
<212> DNA
<213> Stealth virus
<900> 27
gbbmnkbcga attcctggaa gtcgattgga ttgtcagcat gcgcgccacc attgatgatg 60
ttcatcattg gaactggcag aacatgggcg ttgacgccgc caacatagcg gtagagtgga 120
aggccggttg cctgtgcggc agccttggcg acagcaagcg aaacgccgag aattgcatta 180
gcgccgagat tgcccttgtt tggcgtacca tcgagatcaa tcagtgtctg atcgatcagc 240
agctggcttt cagcatcgat accggcgatt gcgtcgaaga ttttgccatt gaccgcttca 300
acagcctttt caacgccctt accgagataa cggctgccgc cgtcgcgcag ttcgacagct 360
tcgtgcgcgc cagtcgatgc gcccgatggc acagcagcgc ggccaaaaga gccgtcttca 920
agcactacgt caacttcgac ggtcgggttt ccgcggctat cgagaatctc gcggccaacg 480
atgtcgatga ttgcagtcat aggagcaggt ccttcccagt agattgcctc gctctttgtc 540
gagacacatt gaagaaatcc gatttcacat cttcattata gaaataagag gcagaggaaa 600
atcccccgcc tgtggaattc ctgcaagccc ggggggatcc acttagttcn taganacggg 660
ccggcaaccg cgggtnggaa acttccagct ttttggttcc cttttanntg aaggggttaa 720
attggcgccg cnttgggcgg taaatcantg ggnccattag cttgggtttn cctggggtgg 780
naaaattggg tanttccggt ttcaccaaat ttccncwhan rmamhadata ragrahntbw 890
hnmartndat nstathbcdc gtmsnwrman symbarahmb cwhnmartnw hnmartnhdd 900
tbcbwhnmar tnnrmawhnm artnmcrstw rdsmdhccdb mbcttdgdan abdaartntr 960
ywkdtabwrd dcmntsmmar ynrmatndcm ntsmmarynr matndatdcm btathbcdcd 1020
mwnstathbc dcdatnstat hbcdcccmcr stwrddcmnt mswrddcwrd dcmnt 1075
<210> 28
<211> 896
<212> DNA
<213> Stealth m rus
<900> 28
gtbbtmnbcg aattcctgga agtcgattgg attgtcagca tgcgcgccac cattgatgat 60
gttcatcatt ggaactggca gaacatgggc gttgacgccg ccaacatagc ggtagagtgg 120
aaggccggtt gcctgtgcgg cagccttggc gacagcaagc gaaacgccga gaattgcatt 180
agcgccgaga ttgcccttgt ttggcgtacc atcgagatca atcagtgtct gatcgatcag 29~
CA 02282858 1999-08-24
WO 99/34019 PCTNS98/27744
cagctggctt tcagcatcga taccggcgat tgcgtcgaag attttgccat tgaccgcttc 300
aacagccttt tcaacgccct taccgagata acggctgccg ccgtcgcgca gttcgacagc 360
ttcgtgcgcg ccagtcgatg cgcccgatgg cacagcagcg cggccaaaag agccgtcttc 420
aagcactacg tcaacttcga cggtcgggtt tccgcggcta tcgagaatct cgcggccaac 480
gatgtcgatg attgcagtca taggagcagg tccttcccag tagattgcct cgctctttgt 540
cgagacacat tgaagaaatc cgatttcaca tcttcattat agaaataaga ggcagaggaa 600
aatcccccgc ctgtgaattc twhattnrma mhadatarag rahntttttv whnmartnda 660
tnstathbcd csssstgtms nwrmansymb arahbcwhnm artnwhnmar tnhddtbcbw 720
hnmartnnrm awhnmartnm crstwrdmmd hccdbbcttd gdanabdaar tntrytabwr 780
ddcmntsmma rynrmatndc mntsmmaryn rmatncmbmc rstwrddcmn tmswrddcwr 840
ddcmnt 846
<210> 29
<211> 5331
<212> DNA
<213> Stealth W rus
<400> 29
gbbsnbcgaa ttcgggttca tctgggcggg acgaacatta tagaagccct ctggtgcctg 60
acgatcaccc tctacgaatt tcggcccaag cttgccagac catttgcaga tttcataaga 120
agcaatctgg tcgtatttgc cgttgttctt ctgcttccag acttcgagga cgccttcttc 180
cttgaaaata cgaaccatca ccggcgaagt gcgcgtcatg cccttcgttt tcatcttggc 240
gacgattttt tcggaaagag gtttttcagc gcgtaagctg agatcggaaa cggacgagcc 300
ttgacagccc gcaagcagag cggatgccaa gagtgttcca agaagtgcgg ttctgatctt 360
catatcgcat cgagcctgtc agagcatttc cagcaaaagt gcgaagcgat tttgcatcgg 920
ataatgcgta aaaacaaata ggtagagcaa cgagtactca gctttaatca gagcctgccc 480
gaagccgcgt cttctgacgc atttgagcaa acctgacttt tcggtgcccg gatattaaca 590
actaaacctt tcagtatcgt tgataaaccg ttgctcaatt acctaaaaaa caccgtgtcc 600
gcaatatggc ggaaatgacg gcatgatgca aatccggcgc acatagtggt ctaattctga 660
catttgcttg ccagtgatac ggacgctgag caaatgtcgg aattatcaag atcactcaaa 720
tgcttaagtt tctagtggag tgaatttgac gtttgaaaca gcatttatgt cagtcgggat 780
tcaaacgtca aattcactcc actagagcgc cgtgcgcctt cttgggcgca caaaggtcgc 840
tctaacgctt tatatttaca gcttaatttt accttaaact gatgcaagtc taaggaatta 900
tgctgtagtg gcgcgccgga gccaaaaacc agttttatag taaattaaag gttacgaccg 960
atatcgagga acttctggcg gcgttcctgc ttcagcgtct cgccatcaac atccttcatc 100
gaacgcagtg aggcggtaat aatgtcgcct gcagcttcaa tcgtggattc cttgccgcga 1080
tgtgcgccgc cgagcggttc cgggatgatg ccatcgatga ctttgagatc gaacagatcc 1140
tgcgcagtga tgcgcatgtt ggaggcggcg tccttcgcac gagtggaatc gtgccacagg 1200
atcgaagctg caccttctgg cgaaatcacc gaatagatcg aatgttcgag catgtagacg 1260
cggtttgcga cagcaatcgc gatcgcgccg cctgaaccac cttcaccgat gatgatggag 1320
atgacaggca cgcgcagctt gaggcattct gcggtggagc gcgcaatggc ttctgcctgg 1380
ccgcgttctt ctgcacttac gcctggataa gcgcctgctg tatcaacgaa agtaatcaac 1990
ggcagctgga aacggtcagc catttccatg atgcggacgg ctttgcggta gccttcagga 1500
cgggccgagc cgaaattgtg cttgaggcgc gtcttggtgt ccgagccttt ttcctgaccg 1560
agaatggcaa caggctgacc attgaagcgg gcaaagccgc cctgaatggc ttcgtcgtta 1620
gcaaactggc ggtcgccggc aagcggcgtg aactcagtga acagccggtt gatatattca 1680
aggcaatgcg gacgatccgg atggcgggcg atctgtgcct tctgccatgg cgtcagcttq 1740
cgatagatat ctttgagcgc atcggccgat cgtttctcga gacggctgat ctcgtcactc 1800
36
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
atctcgacgc tgccctgttc ctgtgcgagc tttttcagct ctaggatctg gccttcgagg 1860
tctgcgacgg gtttttcaaa atcgagatag ttatacatcg ggcctgacta ttgtgcgttt 1920
ccagagatgt tggccataga acaagcccaa tagaggctgt tttacgacgc cttacatatt 1980
tacttcgcgc gcatcttgca aatttttctg aaattctctt acccgccgcg cgcttaatcg 2040
gcaagcggat gatgttcact taccagctta tgcagtcttt cttccagaac atgtgtgtag 2100
atctgggtcg ttgaaatgtc cgcatgacca agtaattgct gcactgtcct gaggtctgcg 2160
ccattctgta aaaggtggct ggcaaaggcg tgacgcagca catgcggcga gatggatgcg 2220
ctcgaaagcc cggcgcgggc agcaagactt ttgagttcac gaccgaaaac ctgtcgcgcc 2280
agatggccgc tttcagagaa agccggaaac agccacgggt tatcgtcgta gcccggcagg 2340
gaatcgcgca atgaaagaaa gacctgcaaa gcttcgcgcg ctttttgcga caggggcacc 2400
atgcgatcct tggacccttt gccgcgcaca atcagaaagc gatggtcggt gcgggcgaca 2460
ctgacgggca ggccaacaag ctccgaaaca cgtaatcctg tggcgtaaag cgtttcaagc 2520
agcgcgtgaa ggcgaagcgc tttgatacgg tctgctggct caagcgcctc ttttgcctca 2580
aggtcggcgc gatcaaggag gcgaccgaca ttttcaacgc tcatgatttt cggcagcggc 2640
ttctgttttt tgggtgcatc gataacgccg gtcggatcgt cctgcctgta gccttctgaa 2700
tagagaaagc gaaagaattg tctgattgtt gaaaggcggc gcgcctgcga tgtcgcagca 2760
aagccttcat tggccatgcc atcaagcaca tggcgtatat cgtcggtttt cgcctcagtc 280
atattgatgc cgcgtgcggt catgacgtcg gctgcagatt ccagatcgcg gcgataggat 2880
tcaagcgtgt tgtgcgcggc cccgcgttcg gcgctcatca tttcgagaaa attctcaatc 2990
gccaaagatg cccgcatgtc tactcctgct tgtccgccgc gtcgggccca tcggtctggc 3000
cgtctgtgac ggtttctgac ggcatcgttg ccggtgccga cgccggaggt ggggcaacga 3060
ctgtttgctt cagttttgac gccgggattt cgacggtgat ctcatgcgtg acgggcttca 3120
cgaaattggc gagcgagaac attgcgccgt agacaatggc agcgatcaca gcaagcagga 3180
caagaatgcg cgtcagcgtg ggcatggtgc gtttatgctg tgctattgag acgaaagcaa 3240
ggacagccaa agcgcgtgca taaaaagccc tatttggtgc cgttcaggcg atgaaagcga 3300
ttgacgccgc gcggtttttc atgtggaacc ggaggaaatg gatgaggttt atgagcagta 3360
caacaaaaca gacaaatctt aacgagaagg cggacactgt ccgtcagctt cttggtgcga 3420
aagtggttgt tcttgttggg ctgatgggcg caggcaagtc gacagtcggt cgcaaggtcg 3980
caacaatgct cggcctgcct ttccgcgatg ccgataacga gattgaatct gccgcccgca 3540
tgacggtacc ggaactgttt gaagcttatg gcgaagctga gtttcgtgat ctggagcgca 3600
gggttatcct gcggcttctt gaggatggtc cgatggtgct cgcaaccggt ggcggcgctt 3660
acatgaatgc tgaaactcgt gaggcaattg ccgcaaatgg tgtttctgtc tggttgaatg 3720
cggaactgga tgtgctgatg gaccgcgtgt ctcgccgcca aaaccgtccg cttctcagga 3780
atgatgatcc gcgcggtgtg atgcggcggc tgatgaatga gcgctatccg gtttacgcgc 3890
tcgccgatct gcatgtgatg acgcgtgatg acaagaaaga agtgatcgcc ggagaactga 3900
ttgacgttct ggccgagtat ctggccgagc atctggataa gaagtaagtt tagactgctt 3960
tggagtggat tatgactgct gccgatactg ttacggttcc cgtctcgctg ggcgaccgat 4020
cctatgagat cctgatcggc aaaggtctta ttgcccgtgc aggcgaagaa gttgcaaagc 4080
gacttccagg cattcgtgtg gcaattgtca ccgacgagaa tgttgcaaag gcacatcttg 4140
aagcactgac cgacagtttt gcgcgcgctg gcattcaatc cacgcccgtt atcgtgacac 9200
ccggtgaaaa atcgaaatct ttctcgacac tcgaaaccgt aacaaatgcc gtacttgctg 4260
caaggcttga gcgtggcgac gcagtcgtgg cttttggcgg tggggtcgtt ggcgatcttt 9320
ccggctttgt cgcaggcatt gtgcgtcgag gcatgaattt cgtgcaggtg ccaacctcgc 4380
ttctagcaca agtggattcg tcggttggcg gcaagacagg catcaacacg caatatggca 9440
agaaccttgt tggtgttttc tatcagccgc agctggttct ggccgatacc gaagtgctcg 4500
atacgctgag cccgcgcgaa tttcgtgcag gctatgcgga agtggcaaaa tacggcctca 4560
ttgaccggcc ggatttcttc gcctggcttg agaaaaactg gcaggacatt tttgcgggcg 460
gtacggcacg cacagaggcg attgccgaat cctgccgctc aaaggccgca gtcgtggcac 4680
37
CA 02282858 1999-08-24
WO 99/34019 PCTIUS98/27744
gtgatgaacg cgaaaccggc gaccgcgcac tgcttaatct cggtcacaca ttcggacatg 4740
cgcttgagac ggcgacaggc tacgattcaa gccgtctggt gcatggtgaa ggcgttgcca 9800
tcggcatggc tttggcgcat cgtttctcgg tcaagatgaa cctttgtggt attgaagatg 4860
cggaacgtgt ggaagcgcat ctgaaggccg tcggtcttcc gatttcgctc aatgatgtgc 4920
cgggcggttt gccggatgct gaaaagctga tggattacat tgcgcaggat aagaaagtag 4980
cgcgcggcgc gctcaccttc attctgacgc gcggtattgg ccaatccttc atagccaagg 5040
atgtgccacc tgcggctgtg cttgaattcw ha*ywvtsrn rmamhadata ragrahntcw 5100
hnmartndat nstathbcdc hgtmsnwrma nsymbaraha bcwhnmartn whnmartnhd 5160
dtbcbwhnma rtnnrmawhn martnmcrst wrddgkdhcc dbabcttdgd anabdaa*rt 5220
ntrywvtabw ttwwrddcmn twdatnstab smmarynrma tndcmntsmm arynrmatnc 5280
mbcatnatns tathstathb cdcmcrstwr ddcmntmswr ddcwrddcmn t 5331
<210> 30
<211> 552
<212> DNA
<213> Stealth virus
<400> 30
gbbmnbcgaa ttcgttgaaa atcttgaaaa acatgaaaac agaattttaa atcaccctgg 60
nnttgnnnct ttngnntttt tttgggtttn aanagatttt ttannatnnn aaagggtttt 120
tttagggtnt tnaattttaa ggggggnnat ttnnagaagt tgntgatttg aaattaanat 180
tgtacaaaag tcaaaacatt gcattattag gatcaaatgg agctggtaaa accacaacag 240
ttgaaatgct tgttggtatt cttaaaccaa gtgcaggaaa tattaaatac ttttttggcg 300
actcaatgga taaaggaaaa attgatgcaa caaaaattgw wnrmamhada taragrahnt 360
whnmartnda tnstathbcd cgtmsnwrma nsymbarahb bcwhnmartn whnmartnhd,420
dtbcbwhnma rtnnrmawhn martnmcrst wrdbdhccdb bcttdgdanb cddaartntr 480
ytabwrddcm ntsmmarynr matndcmnts mmarynrmat ncmbmcrstw rddcmntmsw 540
rddcwrddcm nt 552
<210> 31
<211> 386
<212> DNA
<213> Stealth virus
<400> 31
gbbmnbcgaa ttcaacacca acggctctcg cacgcttgca accgtcgttg ctgagccgct,60
ggaacgcggt tttggtctga cgcttggtaa cgcactgcgt cgcgtgcttc tgtcgtcgct 120
gcgcggcgct gccgtgaccg ccattcagat tgatggcgtt ctgcatgaat tcwwnrmamh 180
adataragra hntwhnmart ndatnstath bcdcgtmsnw rmansymbar ahbcwhnmar 290
tnwhnmartn hddtbcbwhn martnnrmaw hnmartnmcr stwrdrrdhc cdbbcttdgd 300
anbcddaart ntryctabwr ddcmntsmma rynrmatndc mntsmmaryn rmatncmbmc 360
rstwrddcmn tmswrddcwr ddcmnt 386
<210> 32
<211> 1643
<212> DNA
<213> Stealth virus
38
CA 02282858 1999-08-24
WO 99/34019 PCT/US98127744
<4ao> 32
gbbc****** nnnmbctcga ggtcgacggt atcgataatc ttgatactaa attgatttca 60
ttcattttaa ttgcttctaa ttctaagttt atttttgaaa tataagctat cttttttatg 120
tctgtttcat agtcattatt attaacttta tttcatcttt taatagcatg gtctgaaacc 180
ataatatcaa aagtttctat tgctttatct cttatttctc taaagaattt tgcataaaca 240
tcatgcttat atcatctttt aatttcattt aattcttctt ttgctaaatt ttttgaaccg 300
cctggattat attccattgc atattcttct aatttattaa ttggtaaagg atcaaaagct 360
ggaatatagt ctttaggaac taaattaatt ttagcaattt catttggttt gaatgtttcc 420
atgataactt ggtagtcaca attatctaag gttaaagttt cttctttaac aattacatca 480
aagtaaataa atgctccata tttcttttct aattcaattt tttgttgaac aatttcatta 590
aatttttcat ttaaaactgt tttgccactt agagcaatta gcataggttt tgaaattggt 600
tttgagtgtt taatttgttc attcgttgtt aatttaattc aatcaaattg aggataattt 660
ttatccaaag ttgtaatact tgattttact aaagctttca tattaactcc ttttataatt 720
aactcaattt cttattaaat atagcataaa acaatggttt tggtaaaaaa ttaatttgtt 780
taattcaaat attttttaac atttttatat gactttctat gaaattcaca gatgccatat 890
tga~ctcattg ctgcttcatg ttcttttgta caatagccct tatttttctt gaaattatac 900
ataggaaatt ttttgtcaat tccaaccata attaagtccc tagttacttt agctaaaatt 960
gaagctgctg ccacattaat acttaattgg tcacctttta ctaaattaat ttgaggtata 1020
ttgatgtcat taattttttc aaaatctgta attactaatt caggttttgt attaagttta 1080
ttaatacacc tttgcatgcc aattcttgaa gcttgctttg gatttagttg atctacttct 1190
tgagcattaa taatagttgt tactgtttca atagcatttt caagaataat ttctaacgct 1200
tcctcacgtt gtttttgact caattgttta gaatccttta ttaaaggatg gttaaaattt 1260
tgaggcataa taacacaacc aactactaaa ggccctgcac aacaacctct tcctgcttca 130
tctaagccta caattaattt agtgtcagga taattttctt tttcataatt caacataatc 1380
aaaattatac aaaaaaagca aaacttgaat tcwhanrmam hadataragr ahntwhnmar 1940
tndatnstat hbcdcgtmsn wrmansymba rahhbcwhnm artnwhnmar tnhddtbcbw 1500
hnmartnnrm awhnmartnm crstwrdnnh dhccdbbctt dgdanbccdd aartntryda 1560
tnstathdkn m*tabwrddc mntsmmaryn rmatndcmnt smmarynrma tncmbmcrst 1620
wrddcmntms wrddcwrddc mnt 1643
<210> 33
<211> 1033
<212> DNA
<213> Stealth virus
<400> 33
grbbrmnkbt gaattcaaga acgattacaa cagattagac agcggatgaa acaggtgaca 60
gaggatgtca cccaattgag tgagtactca aaaacccatc ccttggcagt tgaggtggtt 120
aaatccttac gaaagactac ccgaacacta aaaaacctcg aagagcgatt actaacaatc 180
ttggatcagg cccaaaagtc taatcgaatc attataaact cgctgaagcg catagaaaaa 240
acgtgcatgg ctctgagcac gaaaaatctg caggatcacg gcatgcggta ctgcattgcc 300
gaagcccgag gcctactccg cacacatcaa gggatttctg ccatccctcc ttcggctatc 360
gaccacctgc cgagtaacgc ggagtccaag ctacgcaact tcctcaaaac gtttcgcgaa 420
scgccgtgga acatagcgaa ctccagatga gcgccgttac ggataggcag caacagatta 480
ctgttcccga agtgttgaca aaccgctacg caccctcgaa tcagacaaac gacatattaa 540
actggtatat tatgtcaaaa gaccaggcgc agatgaacat cttgagttcg attcacccag 600
aagcccggta tgcgtgatct ccccgccatc ctaaaacatg aaaatctatc aagcacgtta 66~)
cgatcaaacc cacagccgat ttggcccacg ggcgggaagt caatgtgtct gcaactgttt 72~~
39
*rB
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
tatgtacata cacgcccttc acctgaaagt gcngcacacg acgctcggta ctgacaccta 780
gatgagatat tgacgaagag cgcattrwha rrnrmamhad ataragrahn trrrrtwhnm 890
artndatnst athbtdcmbr gtmsnwzman symbarahmr btwhnmartn whnmartnhd 900
dtbtbwhnma rtnnrmawhn martnmcrst wrdmdhccdb rbtttdgdan bcdaartntr 950
ytabwrddcm ntsmmarynr matndcmnts mmarynrmat ncmb*mcrst wrddcmntms 1020
wrddcwrddc mnt 1033
<210> 34
<211> 1076
<212> DNA
<213> Stealth virus
<900> 34
gwbbw*r*** **btgaattc gctgcgtcag cacgcacttc aaaaaaaatc cagcgacgat 60
agccttggca gtatgagggg aagagccccc ccagaagacg attgancgct aaaaacgagg 120
gaaaggcccg tagtatacgg cgatnaatgt ctatgngctt tttttgtccg tntngcttgc 180
gaaaattgng taagncgccc anagaggtga taaccccgct tctcaacgac atgacgcgta 240
tttcattgca gggaaatngn gactcgacgc gacctgntcg tgaattgcgt catattaaat 300
aggccaganc acatnttgga acccgtcccg gtttcatctg tccatctgat gccgaggcct 360
gctatggcac gaggcctaat actgggctgt gcgctgacat ggctcatatt gaaaacaacg 420
gcatcttcaa tacaatatcc agatatagta ttggagctta cccgtcgacc ccttaaattt 480
ttacaagaca attccacaaa atgcgacaac aacggtaccg cacgaaacat cagtacagtc 540
aaagaaaacg ccataagctt caatttttac aacanaaaag acgactacac ccgtcttcca 600
gttacctcga tgccttttca ccggtacctt agcaggaaag cttttttaaa accaagtggg 660
atctgtccaa agnaaacttg gaagactacc ttcaaaacaa cttaaacgtc ttacgctaca ?20
agttcttctt caaggataaa ctttccaatt accaaatact tacnggacca aaaancctna 780
actggaacca aaaaaaaacc ttaaaaagga tcaggcccnt tccattcatt acccccwycw 840
wnrmamhada taragrahnt whwwwwhnma rtndatnsta thbtdcvvvv wgtmsnwrma 900
nsymbarahb twhnmartnw hnmartnhhh btbwhnmart nnrmawhnma rtnmcrstwr 960
drdhccdbtt tdgdanabda artntrygta bhwrddcmnt hwwsmmaryn rmatnttwdc 1020
mntsmmaryn rmatnhhdat nstabcmbmc rstwrddcmn tmswrddcwr ddcmnt 1076
<210> 35
<211> 1102
<212> DNA
<213> Stealth virus
<400> 35
gbbmnbtgaa ttcgtacaat ctcacccaag agttgtcgtt agtggaggac gctcggtttt 60
gccagacgcg gcccgtgaac gccgagcgcg ttcgcggtgt cttcggcgcg ctctatcgcg 120
ccgcgtcccc gcacatgcgg gaggagagtg accgcatcaa gctgattttg ggacgcttgt 180
tgctgggacc cgtggccgtg ccctgctact gtgacgaatg ggaggcgaat gactacatgg 290
tggaggcggc gcagttttgc accggccccc tgctgtatgt gcaccgacgc tgccactgtc 300
ccggtatggg gcgcgcgctc gctttcaccg tgatggaagg gcatgtcgcg acgcatgttt 360
ttagagggct gctgtcactc actgagtgga accagcacct gcccgacatg ttttgcccgt 420
gcggcacggt gagcaggcgg gatcggtaca gcatggcctg tctgccgcgc gatcttacgt 980
tttatatcag cgattatcct tactttatgg tggagatcgg gcgtgtgctc accgtgagtg 540
aggtggatga ctacgtgagt cttatgacca gctacttggg cgacgccgtg accccttgcc 600
CA 02282858 1999-08-24
WO 99/34019 PCT/US98I27744
tgcaagtgca ttacaaactg ttgtttgggg tcaatgtcag gcctttaagc cccgctggcc 660
cttgagtttc aacgtgccga attttttatt ttgggaactt tcagaaaaat gtggcttagg 720
gggtggaagt accacaaacc naggtgaccn gcnggatttt tttttgggac ncgtttttac 780
ccggaacttg gnncaaggga atccgggggc nacccnttca ttgaatggnn ttttggngcc 890
ctgccccwha nrmamhadat aragrahntw hnmartndat nstathbtdc mgtmsnwrma 900
nsymbarahb twhnmartnw hnmartnhdd tbtbwhnmar tnnrmawhnm artnmcrstw 960
rdtdhccdbb tttdgdanbb ccdaartntr ywstabwrdd cmntsmmary nrmatndcmn 1020
tsmmarynrm atndatdcmb tathbtdcdm wnstathbtd cdatnstath btdcmcrstw 1080
rddcmntmsw rddcwrddcm nt 1102
<210> 36
<211> 8691
<212> DNA
<213> stealth virus
<400> 36
ccdbasschc ksmgaattcc tcaggctctt tcttaatctg ggatgctggg atcatggtgg 60
acgtgggagg cacgggtggt ttaataatga tcttggtagg gcagtctgtc ttccgggatt 120
tcttacgtgg gatgaacagg gtttcaggat tgcaaacagg tggtggcatg ggctgactct 180
ctgactgagt aacagcgcca tggggggtgc tgggagcagt ggtggtggtg aggatggatg 240
gggtggtgat ggtgatacct gctgagctat ggtcaatacc agcttgattg acagcctgag 300
ccagaatgtc actgtcacta gcaccaccta agttaaagaa gacacggggg cacttagtgt 360
tttgaacatg gtcacattta ttgagatcca cagcacaagt acaggacaac atcttcccaa 420
ccaaccaagt cccacacaat aatgagtcat acaccaagta catagtgttc atgattatat 980
attgtatatc atagagtata acatagagta tatatatggt ataatatcat acattagtac 590
agttagacaa tggcataggg ggttacaata tattagtaca tcatcaatag atgcaattct 600
aactgtctgg ctatatgggg ttacaatggc agagttatag ggaccagccc atataactgt 660
ctatctgaat gacttactct ggcttatcag tcttgctcct ggtcatcata gggtgagagc 720
tcttggaacc ttccccatca tccccctctt tcttaatctt tccagccctt aggacagtgc 780
caaccacctc ctcttctatc tctgtctcat catcagaatc ctctgctttc tcaccctcag 890
tctcagcctg agtctctccc tgctctgtct caggtatcac catctcactc tctccctgag 900
tctcagcctc aacctgtccc tcttctgcct gagtctcctg ttcctctgct gtctcagtct 960
cttcctctgc ctcactctct tcctcctctg tgtcagagaa aagtaccaca kaatgcagag 1020
ggatgtctgg acttggcaca ttctctggga gcacaccacc agtcacaggt gcatagctag 1080
cctctctctc attttcaatg atgatttccc tgagctcagc catgctccat gactttatct 1140
tatcagtctt ttcaatgcac atcttaaggt acatgtcttt gaccaggtac tgtatcttgg 1200
gtattataag tttcacaatg tcctctgtgg gtaggtgaga ctttgagaac attgtctggg 1260
cagtctcatc acagatgtaa gtagagagac tgttcataat gatagacatc tgctggatgg 1320
gtatatacat gcccaacatt atctcatcat tcttagagtt accttcctta tagaaggcat 1380
tcatggtgtt aaccagcagt gtctcaaatt tggaattttc aatctgaagg tctgtctgct 1440
caccatccag tatcttaatg atgttcagac catagttaat catggtctct ggatcatcat 1500
ggtgaggcag acttctcagg aagatgagtc cctgtgatat gccctgactc atcttaggag 1560
tggtgacaca gttacaagtc atcactgagt atttaaagtg tgtgtatgtt attctgtcct 1620
ggaggtcttt ctgttttatc ttaaccttgt cacttaaggc tgtctcaaac atcttggtca 1680
tcttaactgt ctcatcagct agcttcttaa cacactctag atattgaccc tgcagcacag 1790
gaggcagctg gtaattacag cacatatcct caagggtctg taagataccc ttcccaccca 1800
ggaaaggttc catcactttg cccaggagag caatgctatt gttaacccca tcctgtaact 1860
gcttaaactt cccctccatg cccattctta tgtcattgag ttgctgcagg tgttggtttt 190
41
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
tgatgtctgt gtggtttctg gcaattctga gcttggtctg atacactgtg aagagataaa 1980
ataatataag tatatgtggt ttggtgtatg tggtgcagta taaaaaagac acaacacaca 2040
gtatacttac caatagtttg cacttttctt aagggatccc ctggatcttc atttatgatc 2100
tcctccaggg tcttaaagga ctcatcatca ggcacttctg caaagcccaa cagggggtct 2160
cctaggctca ggatacccct tgtctcttct tccaacagct tctcaaggaa ctgcacagct 2220
ctttcagtgc caggatcctc atgtctatgg gttaacataa agacatgtga gactggggcc 2280
ccatacacac agagttggca cacagtgtta acaaagtctt tattgatatg tatgtgaagt 2390
gttgcattga caacctacct gggcatctta ggtggagatg gtccaggttc aggtccagca 2400
gaggttccct cgccagggtc cccttcagtg tgttgtgggg gctggtcatc agcctttctc 2460
ttggtctgtc tggggtccat ctttacaggt tgcttgctct aaccactgga acatgaaaga 2520
cagactcagt atctgctgcc tctgcctaag cctggtggcc cacctcaatc aggctacccg 2580
ggggactttg agtgaagaca ataacaacat caatgggatt gggcccctta cctcctctgc 2640
tatggggctg aatactcagc cacccgggtc tgtgatggcc ctggctgtac acactgcatc 2700
atcatctcct tcctcgacgg tattacccac ggtgctggca ttaagtggca tggtgctggt 2760
ggtgttattg atgattggac taaacattag ctcaaccttc tggagccaag aggtggatga 2820
ggacgcactg gacacggyca ccacccccgt agaggtctat acsgtggact tatgtgttaa 2880
aacagtctaa aaataaatcc tgwggatgaa ataacgtgtc tgtacatgct taagaactac 2940
ttggcacaat gccaagactc catatactgg cggacagcca gttggcatag ggccagatac 3000
tggagggttg ccaagtgcac cgtcaccaat tggcatgggg ccatgatagc gtcaccagcg 3060
ggcatagggc cagaaagcac cgtcaccatg tggcataggg ccaagctata gataagcagc 3120
gtcaccaata ggggcgtggc tataggaaac accgtcaccg atagggggct gcacccataa 3180
gcaatagctc caccccctta tcaatagcac cgcccattag cattagcgcc tcccataatg 3240
gggctggctc atgtacgtcc agccccctat atatagcatg catatacatt agtaccgccc 3300
accgccatat atagattcta taggccaatg gggggcgtgg caatatggcc gccgtccgcc 3360
atattggctt cctatagatt ctatagcatc cccattgact tacattagtt ggcaagctca 3920
atccgcattc caatgcaccg tccccggcta tggaggctgg atcggtcccg gtctcttcca 3480
atggagctcc tccggcgtcc ccaggcagaa tggcggttcc ctaaacgagc attgcttata 3540
tagacctccc atcaggcacg cctaccgccc attgacgtca atggcacgcc catttgcgtc 3600
attgctcccc ccattgacgt caatggggat gtacttggca gccatcgcgg gccatttacc 3660
gccattgacg tcaatgggag tactgccaat gtaccctggc gtacttccaa tagtaatgta 3720
cttgccaagt tactattaat agatattgat gtactgccaa gtgggccatt taccgtcatt 3780
gacgtcaata ggggggcgtg agaacggata tgaatgggca atgagccatt ccattgacgt 3890
caatggtggg tggtcctatt gacgtcaatg ggcattgagc caggcgggcc atttaccgta 3900
attgacgtca atgggggagg cgccatatac gtcaatagac ccgcccatat gacgtatata 3960
gtaaagacca tatatagata ctattgacgt caatggggga gtggctatgg gcggtattag 9020
gaaggtccat atatggtata tgggaccgcc ctattgggag gggctagtta cgtcaatagg 9080
aaaacccata tatggaatac tatatggcat agggccaata catagtattg aacctggcca 4140
atagccatat tggcataggg ccatattgga tattggctat acattgatca tggcatatag 4200
ccaatayacc ataytgaatt ggcacaggtc cagttcctcc atattgaatt ggctagggtc 4260
cagatccacc atattgaatt ggcacaaatc catatgcgcc atattgaatt ggcacgagtc 4320
catatgcgcc atattgaatt ggcacagatc catgtgcgcc atgttgaatt ggccagtgtc 4380
caaatgcgcc attttgtttt ggcagaaatc cagatccacc attttgattt ggacccattc 9440
caagtccgcc atattgaatg ggctcgatgc caagtcgcca tttgcaattg gcaccatgcc 4500
ggataatttt ggcacagtgc cagatccgcc atctttgctg gcaccgtgcc aagtcgccat 4560
tttgaatttg gcacgttgcc aagttttttt ggctcggtgc caaatccgga ttttcttggc 4620
gccgtgccaa aatcgggatt ttgcgttttt tggaatcccc gaccccgggg ggactgtttc 9680
cacgtggttt ggggtctcta cgaggctccg ttcgccgggt atccgggggg gtattttctg 97x0
aaaaataagt tggcattttg ccaagttttg gactcgaaaa taggccgttt ttcaccatct 9800
42
CA 02282858 1999-08-24
WO 99/34019 PCTNS98/27744
gagcgacccg ttttgacggt caaaacggcg tgaaaaatca ccgtttttta cccgtttgaa 4860
ctggctattt ttttgcattt tacagccctt tttaccaccc attttttacc cgtttggaac 4920
ctatttttta ccctctctcg gacccatttc ggactcattt ttgggcccat ttcttgttca 4980
atttttgacc cacctggggg gtatttttgc gctattacgg accccatttt tggtccattt 5040
ttcacatgaa attgggtcca ttttttgctc gtccgagacc ccatttttgg ctcatctgaa 5100
gcccattttt gacccgttcg aaaccctatt ttggttccat gaaataccaa atttttagcc 5160
cacttagacc cattttttag tccacatcag accctaattt tgacccattg aacactcatt 5220
tttggaccat tccgaacctt gaatttggtc caagttctac ccttttttgg ccccattcca 5280
acgttaaatt tcatcccatt ttccgccgtt tttggccact gtccaacccc ttataggacc 5340
cactttcagg cctcttgacg acacatttct aaccccattt tcctccacat caaggcccat 5900
tttctaccca ttttctaccc aatttcaagc ctctttggaa cccaatgaaa ccccgtttta 5460
ctcccataaa acacactcgc atacaggcta attctccaag tttattccgg tctaattagt 5520
gcaacaaaca agcagctcgc gtgtatggtt cgcggtatga aatgtgtaaa cgatttcttc 5580
tggttcggtt aagtttgaga tgctaggcac gtaggttaca ttcatatcag tcgagttggc 5640
agtggttgaa aaacctgaga tgttggttgt cggtggagaa ggagttcgta cagcggtatg 5700
gccaggggta ggcgttggag gtagtggagt taaagacttt agggttgaag gttttggagt 5760
tgtaaacagc gtcttgttgg cagtggcagc ggtattattt tgagttgcgt tcctcgcggt 5820
aatgcccgcc agaagtccat gggtcacagt ctcatttcgt ccgtactcca gagtcgtgtt 5880
cagaaaccag ttaaagtcca taaacggctt ctgtgctttt gccggctcaa cccagacata 5940
gtcaatttta tcagacgcgc ccaggatata ttttgtatta tcatagcgac tagcgcagcg 6000
taccgttcca ttggggcgga caaacagtct gcaaaaatag taacacacag aattgttacc 6060
actctgttaa acgttcataa tctgttctgt catattaata aacaaattac ttacgggttg 6120
taattgcagt ccgttaaggt tctgtgaatt ttttctctag ttaaattctt ggccaagggc 6180
atgatgacgc gttctgcatt tgatgcattt ggtggaaagc atatgtcccc aatgtcacag 6240
ctaagtctat ggagtaatta caaagtgtta taatctgttt catcctccaa atggtaaact 6300
tcttttttca gaaaaacaca agagctgata cgtacgagac tgtatggttg ctgcagatct 6360
tgaagttgtt gcagttgcta ggcgagtagt taacactgac catgtggcag cacgcaggtg 6420
ctatggtggt tgggcggtac tttgcgtagg ctgacgacag tactgaaata gcgcagacaa 6480
tgaagagcag attcatacta acttcaactg ggtattactt tcgaggaggc ttcgcggtaa 6540
tcttgggagc ttcttctccg gcgaaaaggt ttgggcggac gcagatggtg ttgggctttc 6600
tagttataga agttaattcg attctcactt ggaacgccaa ataaccagag gcccgcaccg 6660
cccaggtggt cactcgcatc tgacaggtct gtgcgtcggg accgtcttta acgcggtacc 6720
gaagagtctt gatgttcttt ggtatcatgt gagcaccaaa tatttctctg tcattatctg 6780
tgacattaat tattttggtg ggcgacgctg ccgcttccgt aaagcgttga aagacagcat 6840
ggtttcgacc actgcgaata attcaacaac gatcattaaa aagttattct cacaatgtat 6900
gcattgtgat atcacgctat ctcaacctga gatcttacct gaggtagtgc gccagtttcg 6960
tcacccatgg agagggccgt tcaatcagat gttgacccga cttcgtatgt aaaacgtaca 7020
gcgtactgtt tccgcatttc gggtttggtt tctcaatatc gtaagatcga aacagcccga 7080
agtcttgtgg aggagatggt tgcgcgggac agagtttatc caagtgcaga tctagaggag 7140
tcattaagcc aaagagcaga cacagaacgc agacgcacag ttgcatatag ggagtcattt 7200
cttttcgttc ggtaaactga tagatatgaa aaggtatcgt ttcgagtagc tgtgacctga 7260
attggcgttg aaggtaatga ggcttcgctg cacaccgctg gcgacaggtg ggagcttcaa 730
ggttgttttc aatgctccgt ttgtgtattg gatagtttcg aaaacttcct tcaggtcccc 7380
ctgcaggctt tttgcaatcc ctggcgctct attctgaaat gcgttcacca agagtgatac 7490
ctccgtgacg ttgattctga aatatataca gagtggtgat gaacacgcct attacaagcg 7500
caacgctgtc acatgtatta tgtaaaccca acgtacctct gtaacacgtc cacgccatcr 7560
cggccgtggc tcacatcata gtggtacagc agagtcgtgt taatgatccg tttcaaaaac 7620
tcgtttcgac gtgtctcacc gatgacattg gaacagagat cccagtaact atcctgcctg 7680
93
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
tgatgcggag tgaaattcgc atacaattcc gaacacaacc cgtgaaccgc ggtcgcgcaa 7740
cacaacacag agacacagat aaacacacac catgtaccca tgttgtgttc taaaaaagct 7800
ttattgacag aacgttattt atagctagtt gtcatattct ggctctttca acgtcacttc 7860
ttgggtgttt actttaatga ccttaggtat ctcccacgaa tccataggtt cgctcatggc ?920
ttggtaagcg agttcattat agatggacat gtagtaatgg atgttttctt catcatcggc 7980
tttggactcg atcatcatag gagagtgacg cccgtagttt gggttgacga gagagatgag 8040
gttccccttt ctatcgaagt acatgacgtt attatctgcg tcatcgtcgc tggtggagtc 8100
ggtttctgat tgtcgcaact gctgatactc gtggtttctg gtattggtct ttctttcgca 8160
agagcgccgc ttgtcttccc tgagcaatgt cacagcttct tctttatcac ccgagtaatg 8220
cgtcactaca ttgcgagagg agaacgtact atatagcgcg gccaccagga ccagaagtaa 8280
acagagaagc gctacggccg aggcgcagta gatgacgatg cccaacagtt cgcccagcac 8340
aatcgatgat gaggcagttg ttgctattgt agtcgagacg gttgcggtga cgttgccggt 8900
agtaacattt gtagatgtgg gtttcgttgt cgtcactgtg gtgttgttgc tgccggcggt 8460
agtcatttca g.cggtctgat acctcagggt ggtttataag cacccaggca cgtggttgcg 8520
ggaaggcagt tccacgtggg tattactgag tttgcggggg acgttttaga agtgcaccga 8580
gaacgaaaat gagcaccacg gtgatcacga aggggttgtt ccaaagctgc ttcaagaatt 8640
c 8641
<210> 37
<211> 1213
<212> DNA
<213> Stealth virus
<400> 37
gtbbtgagct caggccatgt taacttgtta ctctcaccta aaacgtgtta gcatttacga 60
tcccctgaac attggtgtta actgttttga ttaaacactt gactctttgt acccgcgtgt 120
catgtgtggt gtatctgaga tgagggcccc gcaacatatt tagaggkgtg ggctcttcac 180
gaacgatcga gaactatgcg acttcgttcg gaagaaacgg agacggttcg ttccatcttt 240
ctattacgrg tttacattct catgtggatc gagggcatgc tcttkttgag cacgtgcgca 300
ctctgctggc tggtgttgcc agagcgcttt gtgcaccttt taccgagtat tcgtaggacg 360
ttattttgtt taatgctttc tattatctgg ttgggaatac ttcactgggc cgagcctcag 420
tttcccaggg agctgtacgt cttgttgact tacacgttca tcatggccgt ggcgatcacc 480
gcgtcggggt ttcaattcgg aaaccgctcg accgtctacg ccatgttggc tattatyttk 590
ctgtttathg ttctgaccct atccacgcat cgctttgccg gagacgtaga gttctacaga 600
ccgttgatag cggcctcgtc ckttctcatt ytagtcctcg caatcctttt ytactkcttt 660
cccgaagaga tcggagaaat tgcagtaatg attggmggtt taawagtctt ggtcacatcg 720
gtcatctgtg agactcaaga catkttacac cagwtagwtt acgtwagcta tgtcccgggt 780
gcgatktwtt tttacatcga catyatttth attnrmamha dataragrah ntttttvwhn 890
martndatns tathctdcss sstgtmsnwr mansymbara hrsagagctc aggccatgtt 900
aacttgttac tctcacctaa aacgtgttag catttacgat ccccwhnmar tnwhnmartn 960
hhtgagctca ggccatgtta acttgttact ctcacctaaa acgtgttagc atttacgatc 1020
cccgwhnmar tncnrmawhn martncmcrs twrdtcdhcc dtagagctca ggccatgtta 1080
acttgttact ctcacctaaa acgtgttagc atttacgatc cccttdgdan daadaartnt 1140
rytabwrddc mntsmmaryn rmatndcmnt smmarynrma tncmbmcrst wrddcmntms 1200
wrddcwrddc mnt 1213
<210> 38
<211> 1198
44
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
<212> DNA
<213> Stealth virus
<400> 38
gbbg*kkgaa ttcgatcgga taccccgtct acgtgtatta atattacata aaataggctt 60
ttttttaaaa aaaagaaaag aacatttttc actaatggtg tcatatcatt ataataaacc 120
ttgttttcat caggaaggta taaaaacaaa ttcatatgca ctaaataata tagattcaaa 180
acaaataagg caaaaatcaa tggcaacaga ataagcatat atataaacat ggtgaaaaat 290
tacatataaa caccaagaat gtggaagatt tagctgtgat tagcaaattt tgcctaatgg 300
atatatatgt ataaacttgt cccaatatct acagagtact cattcctatc aaacacaaat 360
aaaacagttc ttaaaaattc agtacatatt gtgtcaattt taaaaataag cttcaaagtt 420
ttgatactat aatttagaaa ctatctcgag ggaaataata taaatagttt aaataaaagt 480
gaggtgaaac taatgtatat ttagatgaag cagttatagt tttaaattta catattataa 540
aagaagaata ttaatgaact aaacatacat cctaagaagt tagaaataga atagcaaaat 600
aaactcaaag aaagcataaa aaaagaaact ggtggaacgg gaaacacacg tagacggggt 660
atccgatcaa gcttmwmwnr machmhnhad ataragrahn ttntrrncwh nmartnmdmy 720
sskdcwhnma rtnmdaskdc whnmartnda tnstathskd chasrttwns hasrthasrt 780
cttrhasrtc ttrgtmsnwr mansymbara hyyagaattc gatcggatac cccgtctacg 890
tgtattaata ttacataaaa taggcttttt tttaaaaaaa agaaaagaac whnmartnmd 900
whnmartnhh tmgaattcga tcggataccc cgtctacgtg tattaatatt acataaaata 960
ggcttttttt taaaaaaaag aaaagaacaa atwhnmartn mdctanrmaw hnmartnmcr 1020
stwrdadhcc damgaattcg atcggatacc ccgtctacgt gtattaatat tacataaaat 1080
aggctttttt ttaaaaaaaa gaaaagaact tdgdancddb crtntrytab wrddcmntsm 1190
marynrmatn dcmntsmmar ynrmatncmb mcrstwrddc mntmswrddc wrddcmnt 1198
<210> 39
<211> 5643
<212> DNA
<213> Stealth virus
<400> 39
bgbbnnnnnn rrrccgagct caccaaacgt tgcggagaca agtcggcgct cgggactcac 60
atccaccgac tcattgcgct cttggatcac gacaaccatc gcgaactgtg caatgtgctg 120
gtcggcctgc tacaccaaac accccacatg tgggcccgtt ccatccgtct tatcggccga 180
ttaagaaact atctacaaca gaagtttctc aatatcttgg tggatagcgg actccagatc 240
gatagtcttt ttgagggttg ttaccacagc gaagcgtacc gcttgctgtt ccagatcgaa 300
aaaacgaact ccacgcctag ctctctagcc tgtgcaagca ccgttttacc tgtcggtgaa 360
aacgaaactg aaggcacacc tgtcccgccg tgtatttaat gaaataataa aatggttctc 420
atgaataaga cggtcttagt ttcgtttttg aaaggacaag tatgagtgtc cccccacaca 480
tccccgcctt ggccgtggac tcgagcctga actttcgtgc ggacctgttt tctgacgaga 540
accgacactt tctagtcgat ttagtaaccc aaagctgcag cggctatgtg ggactgtgta 600
acgccggact tcccatggcc acctatgtac tggaaacgct aattgacttt caggttaaaa 660
ccacatacat gaaaattaag cccattgccg taaaagtgct aaagatctgt attctggcta 720
actacctaaa aaacagtaaa gaattatgga ttgatttgaa agctaaccta gacgagatta 780
attctggtgc aaataagcaa agactgtaca gaggctttta caaactatgt cgtgataaaa 890
actcgatgga cacttaccga aacgtcaccc agcagctaga cgccggagac gtgacaatgg 900
gcgtattcaa acaatccctg actcagatgc gcgagttaat ggaagtctcc gatctacacc 960
cctctgaaaa tctccaacca atgtacgaat ctctcactaa ctacaacctt ctctacattc 100
CA 02282858 1999-08-24
WO 99/34019 PCTNS98/27744
ccccaccctt tacagaccct agagccatcc aaatgtacag caaaaactta agcgatctta 1080
cgaaacgtgc taatagatct tttaatctac taactgaaac aaacaggtcc aaggaaccta 1140
accacgtagt taacgatgtg ctttttttac tatcggccag acacttacag ttccgacagc 1200
aactggaatt agaaatactg gcaaactgga tacttagtaa atgtaactac ctatgcgaag 1260
acctgtattt tgcctacaca caggtcccgg aatgtcggag tacgtttatt aattacgtta 1320
gcggtttaca agccatacgt aaagtaaaag agcccgtttt ccgtcccata ctccacaacc 1380
tgtgcaccct tctaagaaca ttccacgacg ccaacgttta catgtgccct caatatttac 1440
acacggccat ctttttgttg atgcaaagaa tatccaaggt cgcagaaggt gactcgtcag 1500
attcggaccc tgaaaatcaa gaagccacac aaaatagaga cactctcttg agacgctttc 1560
acgaagggga acatatcgac ctagaagccg atcctactac cgccccttca cagaactttt 1620
atttcgcaaa gaacccttac ggtaacggag atttgttttg cctcccggag aaacctagcc 1680
agtttcttag acgcaaagtg tggttaccca agagaacctt ctgtacatgt cattcaaaat 1740
ggaaaacgga acctttgaca aagacgcctt tagcattcca cgtctgtata gcttagttat 1800
ggaaggcgct tccagacaag cctccacaac ggccaagcaa ttctcgcaag ccttagaaaa 1860
agcgccgttg ggacatgcag aaccccgccc cacagatcac agcgacctat tcgccgacgt 1920
ggagatcagg ccacaacaag actcttccga atccacttcg tctgcgccct ctacgtcatc 1980
cgccccttct gctcatcctt caccgaggcg acagagacta gaatcagtac ctcgtcaaag 2040
acgctacctc agcctgcaac aattctcacc ctactccttg gcccgtcaca accgtcgccg 2100
aaggagacgc catcctcccc ctcccccgag aggcccagcc cacacctctc gtcaaggacc 2160
agatgtttcc tcgccatcta cttctggcga ggaccccaga gacagtctag cggacgattt 2220
tcaaagccgg ttgtgaggga ggatgggact ttcagagttt atgaaataaa tgctttttat 2280
tttgtaacat cgtgtatgtt ttttttaata acgcattaac atttacacaa cagatgaagt 2340
aaactttatt tcagtacaaa atgcatgcat tcacacataa gaaacccgac tgcggttacc 2900
gcgctgagaa ccgcggccgg cgcggaacag ccggagacgc cggtttgcca cgcagcgttc 2460
acacacactg tcatcaaaga ggtagcctcg aaccgtctcc tcgcgatcgg aatcgtcatc 2520
ctcagcggtt ccgacaaagg acatttcaaa agctctcatg tcggcaatgc caccgagaag 2580
cttgcacctc acttcctccg catcataggg caacgattgc aagatcagcg aatcggagag 2640
ggcttccagt tcctggggcc acagtctgcc actggcagga ctgtctagca tgacgctggt 2700
aacgcaaaat tgcaggtggg ccttaatact agcatgaatt cgttccacca cttcggccgt 2760
ggtctttggt gcttgttctg attcatcatc gtcatcattg aacatgttca taggatccac 2820
gggttcccta ccgtgcagac aatatggaat tttttccagt ctgacggtgg ccgcacgttt 2880
acgatcgtac cgatggtttt gatgaccttt ctgccccatg acacatgtaa acatactaaa 2940
ggtatcggcc agacggtaaa tgccattaat agacgggtcg aagccgtaga tcacgccaaa 3000
cttgtctgcc aacacgtaga gtctcaccaa aaattctcct gattctaaga tgcagccaag 3060
cgccccgagc aactgattca tgcataccaa acggggaaca catcgtacca ttatttcaaa 3120
acttttgaag gcttcaggtc gcatgacgct gaaacaggtc tcctggaact tgataatatt 3180
gctatcactg ctccaaaggg caaaatgggt gtctatctgc tcaccggcag ggtcattgat 3240
tttataaatg gtatgattat ttttgttcag tattccactc aactgatctt cctcccagtc 3300
aaatttcaac aactgtttga taatctcatt atcataggta attaatggac actgataggc 3360
ctcttccttc tgaagatatt cgcaacgacg cagtccaagt ttcataaagg ccttcatatc 3420
gggtgccaag cagtagacac atttttccat ctcctcgtag caatacacgg caccgctgcg 3980
accgatcatc ataatgattt ggtaagaacc aagtttttta agttccacaa ctccaaaggg 3540
ttccatggct tcctcgcagc acacgtacct tcctaaagaa aaaacagcaa caaagtcatc 3600
tatttatcat tataactccc cctccccctt tcctacccaa ctaaattgga aagttacata 3660
ccttgaaggc acacatcgta atacttggga ctaaaatgac ccaatagagt acgaggacga 370
agctggatca tagcattttc aggccaagca acgtgcaatc tggtcccaga ttctttgtcc 3790
aaaaagtcaa acaaactggc aggagttgca gcatgcaaag caatgcagcc gtaagccatc 3840
aaagtatccc gaaggtcatc catgccgctc accaagcgat aactcatgtg ctgagttgag 3900
96
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
gtaggtgctt gacgagctgt gctcaagctc actgaagtgt gaccaagcca cgctgcatgc 3960
tatttataca tagccctgag ggctcagtcg cgaagattcg ttgattcatt gatgtaggaa 4020
aattgagatt taatggacgc acgtatctct tgccgcttca tgcacatctc gtggatatcg 4080
ttctgcatgt gttttcggct ccgttgcaca agtccgccga aaagaccgag cagcataaca 4140
gcggccaaga cgacggcgct caagctgaat ataccccaag cacaccaaga aagtcgagga 4200
gaagtattgg catatgtcca catctgagtc acttgagtcc acgtaggcca ttccagtatt 4260
ccatacgtga tattgtctgt tatgttttca tgagtcactt ttactggcga tcttgtgaat 4320
tttttcagac gattaagcaa tcgcaaacac acgtcactca aaaaaaagcg atccgtgtcc 4380
gcgtgaattg ttaaccaatt gaagatactg gcagccaacg cttcggaaac attaccgttg 9440
aactcggtaa tgttttcgcg tctccacgca agtgccgaat tccgtcgatc gcggcttgtc 9500
acactcaaca catttcgtcc ccacgcttcg ctctccaaca caatttcacc ctgagtttcg 4560
ttgtgattgg aagcattccg actacattgc agactgccca taaacggcgt gactcttgac 9620
agattgctta acacgtatag gcggtgcata actcgcccat tcagatagta ctgcagaccc 4680
acacgtaaaa ccatgttatg ccaggcccga gtagacctac gaaacgtcat attgagtttc 4740
agcttagttg tggctaaata acaggggcct tcatagatac ttgttccgtt gtaagtgcag 4800
ttcagcatgc acgacgctgt gctgctcatg ttgccgcggt actgacagtt gagaacccat 4860
ccgtcaaccg tcagacagag cagcggcatg cagatgcaga cctaaacatc caataaacag 9920
aacactgagt tatccataaa cattcaggtt cacacatctc cactcacact ccaaactgta 4980
aacccattac ctgacacagg cggtaggcgc tcatcacccc caagaagatg agacacacaa 5040
ctgcgtggtt atacaacaaa gccgtttatt acaaaagcac actagtgatt gacagaaggc 5100
gtgtctacag tgacaccaag caatgcgggt tgcacaattc agcaaaaaaa aaatctacag 5160
agatgccgcg ccttccatag ttaaatcgat aatcgtatcg ctgtcgctat cggaatcagg 5220
ctggactccg agcttcttag ggtggggggt agggagcgaa cactgtcgtg tcagtgcttt 5280
cttctccggt cttccttcag tttccggatt gggagtgggg gcgacgggaa taacgttggc 5340
caacaggcta tcgcgatcca caaagggtac cggaattttt ccgtcgcgaa cgcgtctctc 5400
cgcgtctagt agagctcyc* ywvtsrrnrm amhadatara grahntrwhn martndatns 5460
tathccdcgt msnwrmansy mbarahddcc whnmartnwh nmartnhhhc ccwhnmartn 5520
nrmawhnmar tnmcrstwrd hhdhccdccc ttdgdandaa daa*artntr yctabwrddc 5580
mntsmmaryn rmatndcmnt smmarynrma tncmbmcrst wrddcmntms wrddcwrddc 5690
~yt 5643
<210> 40
<211> 2657
<212> DNA
<213> Stealth virus
<400> 40
gbbbbwrbbc cgagctcgac cgggacggcg cgctccacga ggtgcccgcg ggcatgacgg 60
acccggcccg ctgagcgccg gtccggggcg ccccgctcga cgggccgccc cggaccccgg 120
acgatggagc cgggaccacc ggccgggagg gggacccgtg ggctggtaca ccgagcacgt 180
cgtcggcacg grccgcgccc cggcgctgtt cgcgctcgtc gggttcgtcg tgacgttcgt 290
cgtcgtgcgg tcgatcacgc gccgcatccg cgcccgcacc gaggccgccg cagcgacgac 300
cacgggggcg cccgggcacg agcccccgga cgacggtcgg ccgccgtcgg ggcggtccct 360
cctcgggaac gtgtcgatcg ggggcgtcca cgtgcaccac caggtgtggg gcatcctgct 420
cgtgctgctg accggcatgc tcgagttccg ctactccccc gggcacccgt ggtcggaggt 980
gctcgcgctg ctgttcggcg cgggcgccgc gctcgcgctc gacgagttcg cgctgtggct 590
ctacgtcgac gacgtctact ggtccgagga gggtcggcgc tcgatcgacg cgatcctcgt 60.7
cggcggggcg ctcgrcgggg cgctgctcct gtccgcgtca ccgatc,ggcg tgacctcgga 6Eu
97
CA 02282858 1999-08-24
WO 99/34019 PGT/US98/27744
cggcacctcc ggcggctggc tcgcctacac cgtgacggtc gtcgtgcacc tcgcgctcgc 720
gttcgtgtgc gtcctcaagg gcaagctcgc gacgggcctg gtcggcgtgg tggtcccggt 780
cgtcgcgctc gtgggcgcgg tgcggctcgc gaagccgtcg tcgttctggg cccgacgccg 890
gtacgggcgc cggccgcacc ggctcgcccg cgcgcaggag cgcttcgggg cgcgctaccg 900
ggcgcgcagg gagcgcgtac ggaacctcgt cggcggccgg gccgacgacg acccgccgtc 960
ggcataggcc agggccgtca ggtcaggtcg ggcgcggccc gcacgacggc ggccatcgcg 1020
gcggtcgccg cggcgtcggc gtcggcgtac cgccagcccg ggctcacgac ccgcgcgtgg 1080
tcgttgaggg cggcgagcac gtccagcacc gcggtgccca gggcccgcgc gtgcggcgtg 1140
aggccgccgc ggatcttcag ctgaccgagc acgatcgcga tctgcgcgcg ggcctcggcc 1200
gcgagcgccg cctcgtcgac gtcgccgcga ccgagccggt ccaccgcgcc ctgccgaccg 1260
gccgcccaga cgtcctcggg gacgccgagg tcccacgcgg cgaggaggcc gtcgacgaag 1320
gcgggcagcg cgtcgtcgcg cccgtccgcg gcgtaccact cctcgaggtc gcgcagcgcg 1380
tcgtgcccgg agtcgttgcc gaacggcgcg aagtcctcgc cctcgtcgta gaacggctcc 1440
ggcgcgaggg acacgaaggc ggggtggctc gtcgcgggcg acagaccctg gtcggggtcg 1500
tcgaggaaca gcgtcatggg ggcgacccta gaccggcgcg gggcgcgccg tcgcgcgcgc 1560
ccgtcgtcgg ggctgccgtg cggaccgacg gtcccgcgcc gcgggaatcc ctcgatgcgc 1620
aggccgcgca cgtgccaggg tgggcgcatg accgacgcca ccgacgcacg ccccgacgcc 1680
ctggagcggg tcgcgtggcc cgtgcggacc gctcgcctga cgctgcgccg cgcccggccg 1740
gacgacgcgg acgcgctgtt cgcctaccgc agcctgcccg aggtggaccg gtggctcacg 1800
cagcggttca ccgcggtcga ggagtggcgc gagcaccacg tcgagccggg gcggctcgcg 1860
acgacgctcg tcgtggagca cgagggcgcc gtggtcgggg acctctacct cgcggtgcgc 1920
gacggctggg cgcagcgcga cgtcgtcgac cgtccgcacg acgacgaggc cgagatcggc 1980
tgggtgctcg acccggcgca ccaggggcag ggctacgcga cggaagccgt gcgggcgctc 2040
ctgcgggtgt gcttcgagga cctggggctg cggcgcgtcg tggcgaacgc gttcctcgcg 2100
aacgagccgt cgtggcggct catggagcgc gtggggatgc ggcgcgaggg cgtgggggtg 2160
cgcgactccc tgcaccggga cctgggctgg gtcgacggcg tcgtgtacgc gctgctggcc 2220
gacgaggcgc gagcgggcgc ttgaccctga cgcgacgtca gggcgcaggc tgcccgcatg 2280
accgacacgt tccccgcctt cgacctctcc cccgtccccg ccccggggcc cgacgccgtc 2340
gccccggagc cgttccgcgg catctacggc atgccgcagc tcgtgaccgt cccgacggac 2900
gacctcgcgg cgtccgtcga gctcbycbbn rmamhadata ragrahntbb bbdwhnmart 2460
ndatnstath ccdcaaaabg tmsnwrmans ymbarahggc cwhnmartnw hnmartnhhh 2520
cccwhnmart nnrmawhnma rtnmcrstwr dhhdhccdcc cttdgdanda adaa~rtntr 2580
ytabwrddcm ntsmmarynr matndcmnts mmarynrmat ncmbangbrm crstwrddcm 2640
ntmswrddcw rddcmnt 2657
<210> 91
<211> 2969
<212> DNA
<213> Stealth virus
<900> 91
gbbwrbbccg agctcgaaga gatcgtcagc aacgtcacgc gcgaactgca aaaatacggt 60
gcgcggccac tcggcatcgt ctaccgcgac aatgaaccct attcggaacc ttgttcgttc 120
ttcaacacac tgctcacctg cggcatttcc cgcgacatgc gcctgccgcg catgggcatt 180
cgtagctata tcgggacgtc gcgtctgcat ttttccaagc ggaccatgca ggcgcagggc 240
ccgaccgaga tcgaaaaccg cttcggcgcg atgctgtcga tcaaggaata tccgcctttc 300
tccggcccag ggatgctcga cgggctcctg caaatgaacc acgaattcat ctgcacccag 360
tccttcaccc ttgccgacaa accgatcgcc caggagcgca tctcccggct acagcgccag 420
48
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
atccacgcgt cggatgaatc tggcagcacg gtcgagactg acatcgattt cgcgctgaac 480
agtctgctca accaggaggc cgtcttcggc tatcatcatt tcagcctgct ttgcctcgcg 540
cgcgatctag ctggtctcga caaggcagtc gcggaactcg gctcctgcct cacagacatg 600
aacatcaact ggctgcgcga agacctcaac atggaggcct ctttctgggc gcagctgcca 660
ggcaaccatg cctacatcgc ccgctcctgt atgctatcca gcgcgaactt ctccggcttc 720
tcgtcacttc acaatttcgc aacaggaatg gccacgggta atcattgggg cttgccgatc 780
tccatcctcg agacgacgtc gcagacgccc tactggttta atttccacca gcgcgatatc 840
gggcacttcc tggtgactgg ccccaccggg tctggcaaga ccgttgcgat gacattcctg 900
cttgcgcagg cattccgcat ttcgccggaa ccgcgggccg tcttcttcga caaggaccgc 960
ggcgccgaaa tcttcatccg tgccgtcgga ggcgcctacg aggtgctcca gccgggtgtc 1020
gaaaccggct ttaacccact gcaactcgaa aacaacgcaa ccaaccgcga gttcctgcat 1080
cgtctcctca aagctatgct cgctccggcg gatggcggcg gtttctccca agaggaggaa 1190
gacactctag agcgtgcaat cggccgcatc tgccaggagc cgaccgaaca acgcacattg 1200
gccaatctgt ctggtctcct catgggcagg gcacgatccg acgccaacga tctccaagcg 1260
cgtctgcgcc cctggtttga aggtgagaag gcctggctct tcgacgcgcc gcaggatgtc 1320
ttgtccttct ccggtcgacg gattttcggt ttcgacatga cgcacatcct cgataatcac 1380
gaagtacgca cgcccgcgct gatgtatctc tatcatcggc tggacgaatt gctcaccggc 1940
gaaccggtcc tcatcttcat ggatgaaggc tggaagcttc tgcaggaccc ggtcttttcc 1500
aactatatcg tcgacaagat gaagacgatc cgcaagctca acgggatcgt cggttttggc 1560
acccagtcag cggccgacat cgcacgcgca ccgcaatcgc acacattgat cgagcagtcc 1620
gcaaccaatc tgcattttcc caatccacgt gcggacgagg aaagctacat ccggcgcttc 1680
ggccttacgg ccaaagaata cgccttcatt cgcaataccc cacccgagcg gcgaaccttt 1740
ctgatcaagc atggcaacga ctcagtcatt gccaggctcg atctctcgtc gatgccggac 1800
cttgtacgcg tgatgtccgg ccgcaaggag acgatcgagc aatgtgcgac gctgcgtgcg 1860
cagcttggcg acgatccggc taactggttg cctgtgttct gtggctggga gaatgcggca 1920
tgatcaggcg tcttccccta ctccttttcg cgttcgcggc accgcccgcg cttgccgaca 1980
tcccgaccat cgacagcacg gtgstcsatg agcacsacga tcgygaccgg aaaaccaccg 2040
agataggtaa ggtcgwcaag gagcgstacg tcagcaatca garcgttacc tgcgssatgt 2100
atcgccccgg acgaaaarac gatccggtcg gtgccgcgaa cgccaatccc gcggttgccg 2100
gcctcgyccg ccggatcgcg ssccaggagg ggatcgacga aaatcagttc ctggcgctgg 220
tctatcagga gagtcgcttc aacccgtgcg ccaaatcgtc ggcgggagcg atcggccttg 2280
cgcagctgat gcccggcacg gctggtgacc tgggcgtcga tccctacaac atcgaacaga 2340
accttcgcgg cggcgcacgc tattacaagc agcagctgcg ccgctacaat ggcaatgtct 2400
cactggcgct cgcggcctac aatgccggtc atggcaacgt ccagaaatat ggcggtatcc 2460
cgccattcaa ggagacgcag ggctatgtcg ccagcataac gcaaaagtgg cttccggcct 2520
ttggcggatc cga~caagtcc ggcataccac tcaactatgg cggcggagga gcgtacgaaa 2580
gcgcgcgaac cagcacaatg aacgcgatgg ggctgacggc tgcgatcggg gaggggtccg 2640
gcgacgtcat gtcctggctc atgcaactcg gtggtctggg gtccggcacg atccaggaca 2700
gctgggacca caattccggt gcgcgcaatg ccaacctcga gctcycnrma mhadatarag 2760
rahntwhnma rtndatnsta thccdcssgt msnwrmansy mbarahmmbc cwhnmartnw 280
hnmartnhhh -cccwhnmart nnrmawhnma rtnmcrstwr dvvbdhccdc ccttdgdand 2880
aadaa*rtnt ryttabhwrd dcmntsmmar ynrmatndnb wdcmntsmma rynrmatncm 29x0
bmcrstwrdd cmntmswrdd cwrddcmnt 2969
<210> 42
<211> 6984
<212> DNA
<213> Stealth virus
49
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/2??44
<400> 42
ggbbvgvvvv gvbcgaattc catccaggct tttgcttaca gcctggactt ccagactcag 60
ctgcaaaaga ttcgcgacct caaggcacgc tttgccgatc tgattaagca gcagcatctc 120
aacgcgtctg aagaagtacc cttacccatg ccccacctac caggaaacac ggtcatcgcc 180
tccccgctgt cgtttgccaa gggcctggcc gccctagaga aatatgtttt gggcggctac 290
cagtggttaa ccgaatgtat caaccgtyaa cctctagtgt gtcaacgcat agacgacatt 300
cccggccgtt ttgccgtcaa ccgatattga ccgcaagaga gtcgccctag atcgcctcaa 360
gcggctgagt tttagtacaa agaacgaaat gtgttacgaa gttgtcgacg tattcggcct 920
tcaccaactc atgtccaaaa atggcgttcc catacacttt gtactgagct acggaaacgt 480
gtttttcaag tacatggcac tacatcacga tgataagcaa ttggcaaaaa aatttgccca 590
agttaaaaat ttggtgactg gcagatacaa agtggtaacg gtcaatgtcg ccgtagccca 600
gaccttgaaa accttctggt cccagatatc ccaatacgac ctcaaacccc tactctcagg 660
tcaaacactc ataggtttag gagaaactaa cagtctagta aacctaaaaa attttcattt 720
atattgtcgt atcagcctgg aacttgcagt tggatgtgct tcaggaacat cgaggtccgg 780
tcatccgcat gcccatcgat gatttatgta tcgccatcac cacgttttat cccgaataca 840
tctatggcat cgtgaaacac cccattcaaa ataccctatc ttcgctcgtg cgtgttctca 900
aaaaagacat cgttcaggaa gccatcaata acgtgactca gatgccaccc gtctatagcg 960
ccgatgagat caagggattc tgcatcaatc ccaaaatatg gtcatcggtc aatctgagtc 1020
gtgtgatgtg ggaccagaac ctcgtacgcc agatgtgcga cgtcggtccc cgcaagaacg 1080
gggctcagaa actgtggcag tacgccgtgg cgattatggt ctttccacag gatctactcc 1140
agtgcctgtg gctggagctg aggcccaagt tcgccgaaga gtttgcaacg ctcttcgact 1200
tcttccaggc cctttttgta cttttcaccc atcaatatga catcaccagg gagtcgaaca 1260
tgaacaccca cctagccacg ggagaagcca tcgttcagac cgtcggcatt cgacgcaaag 1320
accacaccga caagagtcta ttggacgttt ttattgaaac cgacaccgcc atagattacg 1380
tgttgggatc ctgggttttc ggcatccctg tgtgttgtgc catctatgtg tcagagatct 1940
tgaacggcag ccggctactg ctggctcgcc acattgagta taccgtgcgc gacgcagatt 1500
tcatgcacgt tcagagggcc aaagatctta acctcaacta tgtaatcaca caaacgtgga 1560
cgaacacccc gctagagcaa tgttggtttc aagcgcagat tcaacgcatt aaagaccacc 1620
tcagaactcc cctagaactc gattttattc cattagtcat ttacaacgct cacgacaaaa 1680
caatacactc cgtcatacgc cccccaacaa ccgccgaacg agatgtgtct cgcattgtgg 1740
tagaaaaccc cttccctacc ctgcccctaa tcgacgtccc ggagtctgat ctcgtga.tat 1800
tcgaccgagt tcctatcaac accgactttc tccgagaaga tcccccgccg tgtaccgtca 1860
gcgaggtcgc gccagtggca gcggcgtcag caaaggtggc aaagcccgcc aaagccagtt 1920
caacggctcc taaaaaagtc caggttgtaa aaacccctca ggtggatcga gtgcaggcag 1980
aaggttcgtc ggtggacgtt ccggaattat ccgatgatga ggaagattac gaaatcttaa 2040
cagaggacga atcgtacgag cttatagaac tgtcctcgga ggaagaacaa caatcactgc 2100
cttccgtgcg cacgttcgtc gagcctgtgt tccgccagca acctgtgcag actatcgttc 2160
gtagagaaga tgttattacc gtctccccta ccgccgccag ctccagtttc ccaaatcccc 2220
caatgaccac tctaactcaa aatgttgtaa acgccattca aatcctacga tccgtgcgcg 2280
tagatctt~a atcgatggct aaatcggtta acgaaaccat taaccgtctg cgcttcctct 2390
atctactgta gcgaggagac gcccgctagc gacgggttct ggctaccgcc aacatgcgca 2900
gtaagtccag cttaaaggca aacttgtctg taaagaagct ggacatccgg acgtacttgg 2960
acaacatggt gccggtcacg gggtgttcca tggactcctg gggcagatcc aatacattca 2520
cacacacgtg gcgccgcttc tcctcatcct tcttaacgtt ggtacccgtg ttgctcgagc 2580
tagacgacat gactgctgcc gtgacacacc gtctgcttca ccaaggcgca gccccgacac 2690
agcgagccgc agtcctcgag ctcgagacag ctgtcgcgat attccccggc ctggcaccgc 27~)0
gaacacagcg gcccctggcc gtgacacata agcttcagca gtcgcgggat agtgacggag 700
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
cgcaccacca cggtggaatc gcacgtccgc gcagagcacg gtagaatgat gtcaaacgtg 2820
acgaggtggt catagaccgc acacgcggcg ttcaacccca agactgcctt ccaaccaaac 2880
cgcaaacaac gttgcccaca aatcgtctca gagacaactt cgtaaacacg ttctttaatg 2940
acacgctgac ttccacaaag agaacagtgc accagttcgg cgttagtatt gaaaatgaca 3000
ctcttttctt ggcggtctct ataatagaac atagagttaa gggggaaatt ctgctcgcag 3060
tgcagcttct ccttgcccaa gttcaggcag tggccgcact gtcggcacac cacggcgatc 3120
agcgatctgg cgtctaggtg gcgctcgcac ttcaggcgac acagacacca gagcggaata 3180
tcaataacgc tgcctataag tcctccgcgc agcgccaccg ccagtccgta catcacgatt 3240
ttggtaggtt ccagcggccg cggttgttta tgggcgcgga cctcgtcatt aagtcctagg 3300
gcgcgcagcg gtaccagata cctcgggcag gtgttacaaa acgactgcat ggcttggcga 3360
gccatcacgt ataggggatt cccgcagggc acgggcccgg catggcgacg cagcgccgcc 3920
accagagagc ccagctgaac cgaactcggc ttccgacgtc gcgtccactc gttccgatga 3480
tagacagcca ggtcggcccg tccgtcatat ctcttggcgc gcaggaggga gaggcaagga 3540
gaactggtct gattcagcac gggaagtcgc aggtccactc caaacagaaa gcgatgcagg 3600
tcacccaaag cagaggaggt catgctatcc agcaacgcgc tgagcttttc ggcgggatat 3660
tgctgtagcc tgaggtagac atagtccgca tcgtagcgct caaagcgcaa aaaggccaca 370
gttcgcgaga ctccgtgaaa gcagctcatg ctgtacacgt aggccaggaa cataaagtaa 3780
ggctttgtca tgaccagacg ctgaaacagc gtggtaaccg cctctcgttc cacaggtccg 3840
caggccagcc attcgtgcag aaagcgctgg tacaggcgat ctccgagttc gcggttgaga 3900
aaccgtttgt cggtgacgaa gagttgcaga gcacaagccc gctcctcggt gtaagacgcg 3960
ccacgcccaa tcaccatctg cacgtggaag tgatcatcgt gcacgcagag aggagtgaag 4020
agccgccaga gcgcgctctg gaagtcacga gacatagcga tacagaagga agagtaagat 9080
tcccatcacc gcgccgatca gaagaaagcg caggtcgagg cggaacgagc ccagacgcac 4140
ctgcgtcagc gagcgactcc ctctgctgcc cgtcatcgtt cctcggggct cctcctcctg 4200
gccaccgcag cagccagggg cggcagcccg gcaacgacac acgccataga agccacctgg 4260
cggaggtgga ggcggcgtga ccggtggaaa cggcggaggt gcgatcgtca tccgcggtga 4320
gtgcagccgc ttgcggctgt tactgctctg gtgtctcgag agacccaaac ggcttcgcag 4380
cacggggccg ctggacgcgg ccgccgcctt tttagcacag agttccttca gcaagttctc 4490
gtactcgacc tcgttctcgg gaccgaaggc aatgagttcg atattgaaga ccgagggcga 9500
gttagacttg cgcaccacac acttagtgag caccccgtag gccgagggct taatctcctc 9560
aatatcctta agagtgacaa tcagcgaatc gttgaccttg agcacgttga actcgccaac 9620
gtggcgacac gagacgagct tcaacggcgc tcggacaaaa cagcagagag aaacagcgca 9680
gccggtgttt ttaaagataa aacatggcac gtgatcggtg cgactttccc aatagctcaa 9740
caggtactcc acacaataca ccgtgtccgt ctttaacata gcgtcacata ccgagtaatt 4800
ggggttcttg caaatgagcc ccgcgtcagt aacgcgcaat tccgcgggtc ccagcttcaa 4850
aatgcgtcgt gtggccgaca ctaagtcgtg atgcaaccct ttactgattt ccatgacacg 9920
cgaccacgac cgcgcacgtt ttatttaccc gaagattcct cttttccctc caggatcccg 9980
ttaatgtcca tgagcttatt gacgatagcc gttaatagtt tcgtcttttc ctgcagaatc 5040
tgcgcgtgac tgcaagagga acactccccg tgtacatact tgagaaacgc cgcatacttc 5100
tgacccgcat taacgaaatt caatctcgcg tctagcgacg gcagtaacaa ttcgtaaact 5160
cgcggaagca tcggttcgaa gcgcacttcg aagtcgtcct ctggttcgaa cagtccctcg 520
tcataaggat catcctgatc cagtcgtgcc gaaggagccg ccatcgcacc acccgatacc 5280
agcccaattc ccgcacacac ttttagcccg acgccgccac caacatgaac caccacttat 5340
cctctcgcag ttatatctac accggctggg aggtagacct cacgccgccg ctgcacgaaa 5400
tcacaaatga actgctgtgg cacgcgcacc cccgtcaagt acccgagacc accgcccccg 5460
acacgtcgca atgcggctcg gccgcgggcg gcggcagcag cggcggggga ggaggagacc 5520
gcgcaaccca gagcttcctc tttagccagt cccaatccac cgaccagcta accgggcaag 5580
gcggcggcca gttctgcgac cttgacatgg aactagctaa ctttgagttc tcagatacag 5640
51
CA 02282858 1999-08-24
WO 99/34019 PCTNS98/27744
aacgactgaa aagactgtgc accccgctgg acatcgatac ccgatgcaac atctgcgcta 5700
tcatcagcat ctgcctgaag caagattcag atcaagcctg gctactcgac tacagtttgc 5760
tgtgctttaa atgtaattcg gcaccgcgca ccgccctcag tctgctagtc accatgtccg 5820
agttgactca tcttttgcgt cagcactttc cggacctgca cgtggaccag ctctttcggc 5880
aacatgtctt gacggtgttt gatttccatc tgcatttttt tattaatcgc tgcttcgaaa 5940
agcagttggg agatgcagtg gagaacgaaa acataaccct gagccatttg gcagtggtca 6000
aagccatggt gatgggtgac gagacggtac cgtacaccaa acaccggcga tttagccacc 6060
acaaacagaa aatcgttgtg aaaatcccag aggccccgaa gcaacttcta cagatgttta 6120
cagaacacag cactccgtcc cccgagcgct tcacgtactt gcttttttac atgtggtcgg 6180
gcacgggcgc gatggcgagt acaccgctgt cggaattggt gcagagtaaa caacacctgc 6240
tgaacagcgt ggcggacgcc gacgacccgg agattaacaa agaagtcggg cctgtctacc 6300
tctcccccgt acccgtgttc caagtaaaaa accaaaccag caccgtgtgt ttgctctgcg 6360
agctcatggc ctgctcgcac tacgacaacc tggtgctacg cgagttgtac cggcgaatta 6920
catcgtactg cgaaaacaac gtgaaaatgg tggatcgcat ccagctggca ctagcagaca 6480
tgttacggga atgcgcgatg ccactgagcc cccagtacga ggacatgtcc cggtacgcgc 6540
gcctcccgcc cccggccgac tatctctcca gtccgaccat acgccccgac cccgtgttct 6600
gcctcgtgtt gcggcaagcc ggcgtgaccg gcatctacaa gcattttttt tgcgatccgc 6660
agtgcgcggg caacattcgc atcactcgcg aggaggttct cttcggaaga attcb~ywvt 670
srnmknrmam hadataragr ahntYwhnma rtndatnsta thbcdcgtms nwrmansymb 6780
arahrwbcwh nmartnwhnm artnhddtbc bwhnmartnn rmawhnmart nmcrstwrdn 6840
wdhccdbctt dgdandaada atabcdhrtn tryhtabwrd dcmntvhhsm marynrmatn 6900
mdddcmntsm marynrmatn rcmbatnatn stathwtdcd bcdcatndat nstathmcrs 6960
twrddcmntm swrddcwrdd cmnt 6984
<210> 93
<211> 8579
<212> DNA
<213> Stealth virus
<900> 43
gbbccdbass chcksmgagc tccgttttcc cagcgagtgc gccacatggt agcgattcaa 60
cgttcagatc tggatgaatt cacgtacccc tgtcaagctc ttaaaaggaa agggatcgct 120
gtacgtcacc aaccgtgact gatgcaccaa agctaccagg acgcgttccg taggtctttc 180
tcgcgtcgat gacttcgtcg ttacgaggca gtggagacga gggccagtgt cttcctgatg 240
gctcgctgcc tcgcgctccg ctgcctcgac accgacgatc tgagactcga ggacataggt 300
ctgttgcacc gtatcgtaac ggtgcagcac cagcgtattg ggatctagct tctcccaggc 360
tccctgatac gggtcgaagc gctctgttaa acagagccag tcgtagtgtt tctttaaaaa 420
gtgctggcgg cgctcttccc ggtcgtaggg agccagaagt tcgtggcggc gatccatatc 480
gcgatcgtcc gcgtgcgggc atatgcactg atgttccatt cgaatttttt tctgacgctc 590
gggctcgaag cgtcggtacc cgaacactag tttcagaagc cccatccgaa aaaactctgt 600
gatgctgttg gccacgcgcc gaatgtggtg actaggttcg tctagctgga tggcgtacac 660
cgccccaaac caatccagca cgatcaccac ctcggccaca aaactgcgtc cggggcgcgg 727
tcgcccagtg gcccctagca gataccaggg cgtagccagg ttagccctga tgccccacca 780
ccagcgtttt gcttcgtttt ccgtgaggct gctgaaaggc cacacggccc gcagttctgt 840
cacggttttc atgaggcgca agatgacggc cccgtaaccc ggggtgtaca gcttcacatc 900
gtgctccatg atgcgatctg ccgtgacata aaagctgtcc ggggtggttt cgttgagaaa 960
caagatgtgc atagtgcgcg ggggacgcgg accgaatcgc atgaggctcg gcgacatgcg 100
ccggagctgg ttgtgtatgg cgtcgcgata gatgaactcc gaacgcatga ccccgtattt 1080
52
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
cgccaggtcc tctagcccgt gcgccacgat caccatgtag ttttcgcggg gttcaaaggc :1-10
gtagatgcga cagaaacgac ccaggcagat cacataatcc gtccgtaggt gatcgtgatt 1200
gtgatcgcga tgaggctcgg gtatcataac aacagcatag cccagggcac acagcggctc 1260
gttacagcag atcagtttcc tagccgcctg ctgcgcctgg agcagctgct ggtcgcgttg 1320
cagttgcacg taccagccct gcggaggccc caggcatagc cggcgcccct ggtaatggtg 1380
cacgtactgt tcgatctgcg aagtttgcgt gaaaaagaac agttcccgaa agtcggtcag 1440
cacctgtctg tagaattcca aaccctgcgc ctcgcgctcg ccgtgctcgg ccgacatcat 1500
cgtgagggac gacgatagac gaaaactcac ctcggtctgt taaccgatct agcgttcgga 1560
ccgatgtatc gagatctcgg tccgagctgc tgagcggttc aaagaccagg tttggggtta 1620
tcggcgcctt cgccaagttc tggaccatca tcaggacatc gctacatacc gacgtggatt 1680
atgaacttgt cacgtcagaa ccaatcggac ccatggaagg tccccagggc atgaaataaa 1740
cagacatttg cgaaaacacg gtgcagtcat caaaccactc acatgattgt ttttattatc 1800
agacagttta cagccaaggg ggtaaatata agccgggacg aggcacatct gggcgaggaa 1860
atggacgtcc ttccaaaagg gccgctttgg cggctctctg aaccagcact tgggaatagt 1920
aatcgcaggt cacctctttt gcatcttctt cctcactgtt gctgtctatc tcttcggaaa 1980
cgctctccgt cttcttgctt aaagcggctt tgcccccgtc agtttctaac atatcatcgt 2040
cacagacttg tcttggtggt ttttggggtt tctgtgactt ctgaggtttt gcctgtccca 2100
cgtaaactac aggcacggag tcattatctc tggcagcagc ggccgcggca ccgccgcttt 2160
catccgacaa catcaatcta agcctcgcga tttctcgttc tagctgagga ttcatctgag 2220
tccagatcga gtaacaccgt gtaccctgtc tcacttcttt agaatgcaca tgatccgag.a 2230
gacgccgcca gaaactgtgc gcggcttcca cttcggtagc ttgagggaaa tcacaacgta 2340
ggtgaggctc ccaactggca tcggccgctc cggccacctc gtgatagcta ttgcgaccgt 2900
aacaactacc cgggtggagc gggcgaaaac gatctcgtcg cgtcaaccac ttaaaacgag 2960
tatcgtaact acgatgcgcc gctccccggt ctatgtacag atagcggtcc cagaactgat 2520
aggtgcggtg agggcagtgc gtggccacct ccagcctttc ggcgtcagat agcgcgcggc 2580
tgaaacgccg accggcctgg tagattttca gtaaccccat ggtcaaaaga gaatccagat 26-10
cattagccag tcgacacacc tcgcgacgat acacgtcaaa gtaaaagaat tcaccaaacg ~7~~0
catccatgag gaccacccat tcggcatggt aagatcccga agggagaact tctcccacca 27x0
cgccgaaaat taacacgtca cagcagagac ggtctttaaa gaattgcata agcttcgcga 2820
acatctgatc gtccatacag agaaagggcc aacatgattt caggtcgttc ggctctccgc 2880
agatcatcat cgggcgagtc atctctccgg gggttctgag cggcaggcat tgccagcgat 2940
accgcgccat gacacatttc agatgagaca cggagtgatc gtttagacgc aacatagaaa 3000
ccatgtcatc gggctgcgta gtcaatatgg gcatcctgaa cttgcctgtg tagatactct 3060
cgcagtgcat caaaccgtgt cgcgcgaaat catccaggct actagctagg tagtacagaa 3120
cgtcctcatc ccggtccaac aaccaaagac tctcgtagcg ccccatgagc acaacgcgct 3180
tgcttttaga tggcggtcgt aactcatcct atacagataa ctgtcatcgc actgctcgtc 3240
gccggaatcg tcttcgtccg aagagtcttc atcggattgc tggcgacagc tccaatactg 3300
cagatagccc attacctcca gcggctcttc gcaacagatg agcttgcccc aaggcgagtt 3300
cggaccgctg cacggtgtat tgtccccgaa aatgctcggg aaggtcgcaa acaccatccg 3420
ccagccaggg ggggccgaga taggcacact gatgcggcat tcggctttga ttgacaccag 3480
agtacgaagc gtgctctgtg aatcttgatg agtaaacacg tccttgaacg cataaagcat 35x0
ccgcctgatg gcgggccctg aggcgtaacg ataggactgg cgtagcatgt tggtgtgcca 3E00
ccgcacattg gaatgtcacg ggctttatgc cctctgtgaa atgacgtcgt agatgtgtgc 3Eo0
caggatcacg gcttattaat tgtggtgtgt atctt~cgaa agccgttcag tcggctgcgg ~.~0
gttgcccgac -ttcacgtcag raaaacccag agccgacatg aattccagct gccgtaacat ~ '-.0
aaccgcccta acccctttgg gcccggggcc catcattacg ggttacgcgt gcgtttttct 38-i0
gttcggggt,~_ -ttaggacatt tctatctagg tttcaaaaac agcagacgac aacgc:.aaoc
=°~70
gaatacgttt agcgatattt tattcagaca tttaatgatt acagaagaag tcttcacc~~ ._.._
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
caccatcccg ctgtggactt accatctgat cagcaacggc gacctaccca gcccgtggtg 9020
tcggggttta accttcgttt tctatctcac ggcttttgcc cgcgcgtttt tctacctgct 4080
cctgtcctgg gaccgctaca acatcatcgt ctgtcgtcac ccgctacccg tgcacctgga 4140
ctacactcaa gtggtgggcc tagccgtctg gttagctgcc gcgctggcag cctcgccctt 4200
ctctattttc aacggcgacg tccagcaatg cctcggcaac atgggcaaag tgcccagcca 4260
atcctccgcg accctcaact tggaagtgca catgtgcact ttctggatac cgctcgtcgt 4320
gacggccaac tgttactatc aagccaaacg tcaggcggcg gccgatcaga agatcgaact 9380
tcaaaaatgc gccttactag taaccgtggt tatggtgttt accatcatct ggttcccttt 9440
ccacctggtg ttgcttatag atgcgctggc gagcctcagc cacgtggatc ccacgagcgc 4500
ctgccactgg gcacccatcg tagtcatgtg cgaatgtcta gcattcgcct acgtcggtgt 9560
tagcccgatg gtatacttct tcgcctgccc taccgtgcga cacgagtttt tggtgagcgt 4620
gcgccccttt ttcttaaggc tttcgggtaa gacatgggga ggctacgttc cggtcgacac 4680
acaggcaact gcgaacaaac cagatccaac gaccgaaaac gagtaccaaa ctatgcatta 9740
aataaaaagc cgtaatgtca atcactatgt tctgttttct ctacgttgtc gataacgcgc 9800
aagcctggga ataaacgcgt gctatatgat catacagcat tagtacgtta gtcaccaacg 4860
ctagaacaaa ccatggccaa cagctccgca aacgagtcgt gccaactcaa caacactctc 4920
caggcgttgg gaatacccaa ttctgtaccg atcagcatat acggtctttt tgtagttatc 4980
ggactgattg gaaactttat gttagttttc atattggttt acagacgcaa actcaggttc 5040
cccagcgaca tctactttct gaatgctgcc atagcagaca tattttgcgt ctgcatgtta 5100
cccgcctgga tacaatatgt agtagaatca gtgacgctca atcggttcgc atgcattact 5160
ttttcttttg ggttttacat ttctctgttt ctacaatcgt ggatgctcat ccttatcacc 5220
gctgagcgct attcatcttt agtttggatc gctccgaata aaaaaaccac cgcgattaaa 5280
agatgtgtat gggcctggtt catgtctata tttcttgcat ctccgtattc tatctttcgc 5340
aagtccgatg aagttgaaga atgtctcctg ggaaatttca cctggcacat cggggaactt 5400
taccacgccg ccctggatct gctaatcacc actttgactc tcatcatacc actcgctgtg 5460
ctgctgattt acagtttcag aatcagcaga tccttctggg gaaacagaaa actgaataac 5520
aaaaccagcc tgttcctcat gcaaatcttt gccgttgcgt tggggttctg gggccctttc 5580
catctatttg tgtttataga aaacgtaacg caccacttgt acggcataca acagatttgc 5690
agagtacgat atacgcgaca cctcgtcagt ctgctaacgg aatctctagt atttctacgc 5700
tcagttttta atcccgtcgt ttacctaatc atcagcgcca aatttcgtag acgcgtccaa 5760
catctatttc aacgcattcc atacaccaat ttggaaatgg aaaccgacaa ggtggctgaa 5820
acaatggaac tgaaagccag aggtatggat gtatctgacc ctacacccca cgactacgaa 5880
tgtttcctgt aaacccctac cttgaattaa cttatggtaa caaaacactc acaatcgaaa 5940
aacatgcgcg gcggaacccg gggagcaaat aaccaaccgc aacatgacta cagaaccctg 6000
ccacgtaaac gacactctga gcgcctatgg aataactccc agcatgatca tcagcttcta 6060
cggcttaact gggattattg gttttacggc aaacattgta ataatttatg taatgtgtgc 6120
taaccgcctt gagcggtctg cgcacgatat ttattttata tacatggtat gcacagacct 6180
gagtataatt attacaatac ccatatgggt ttattaccta acaaaccaag acaaaatata 6240
tggttgggaa tgcagtcttc tgtcattcac gttttatgtc cctcttttcc tttatccata 6300
ttttataatt gcaatagcca tcgaacacca tcgaactcta attctagaca agcccgttag 6360
cgttaaaact gcaaacataa gctttgtaat aatctttatt attgtaattt taatatcatt 6420
accctactgc atttttagac aaaccagcgg atttcactca tgtatttttg gcaacaacac 6480
gtggaatgta tctgctcccg ctcgcaccgt aatgggcatt acaattaacg ccttcacata 6540
tgcacttccg gcctcggtgg cgctatttta ttccatcaga atttattcaa cacgccgggg 6600
tagtaaaaag cgaaataaaa gagccagttt ttacatcgac gttatgactg ttaccatgtt 6660
atcttttaac _ggacttatca atctcaccat atttaaaaac atggttgttg gttactcgca 6720
aaacaattca gattgtgatt acattaaacg agaacacttt tttggcatga tgggtataac 6780
ccttgtgttt tttagagctg ctatcagtcc cattatctgt atgtacgtca accggaaaat 6840
54
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
gtttaaaaat ctctgcgatc tataatcatr caacaagatc tagacgcgtg tacgaaacat 6900
aggagggtca actcacaaac cgcaacatga gtaaccaaac ctgtaacata aacgacagtc 6960
tcattgccta cggactgact cccggcgtta ccatcggcgt ctactccctg gccggaatcg 7020
tgggtcttgc gggaaacctg ttgatactct gtgttatgta tcttgggcgt cctaaatggt 7080
tcgcgcacga tatttttttc atgaacatga tgttcacgga cctggctatg attctgacga 7140
tacccgcgtg ggtatactac ctaataaact actcacagct ggaacattgg gaatgtattg 7200
gcctgtcctt cgcgttctat gttcccctat tcgttcactc cgatctcata gtcgcgatag 7260
ctatagaacg ctatcagagc ttagttagaa acaagcctgt cagcgtcaga gccgccacag 7320
taagctgtgt gtttatctgg atcgtcgtca ttttggtttc atctccttat tacatgtttc 7380
gaggaaaaca cgaaaaccaa tcatgcattc ttggtaacta cacctggcat atacccggtc 7990
ctctccgtac cgtcatgaac gtcgcaatta acacatggac atttgtggtt ccggtcgccg 7500
cggcaatgtt cctgtctctc agaattcatt catcttcatg gggcagcaga aaaatgaaca 7560
tcaggaccag cttccacatt gacaccatgg ctgtcaccat gctctttttc aacgggctgt 7620
tcaaccttaa catctttcga gacgtagtgg ccgatgactc acaacaaaaa agttgtgatt 7680
atatgaaaca acaacacttt tttcgcacga tgggtatagc ctctgtgttt ctcagacccg 7740
tctttagtcc tatcatttac atatgtgtca gtcgtaaaat catacagggt atctgcaaat 7800
tgtttataaa agtaccaaac cataccataa gctcggaacg tgtaaagctt atgtctccaa 7860
atagaatgaa cgacgatgcc ccagagcttc cgcccaggga atatgaatcc gcgttctaaa 7920
ttattgcgcg ttgatagcgc aacgacacaa ccagccgata tatgtttgag accggtcaca 7980
aaccccgaca ttgcaaatcg acattgttcg atttgcgaac agacttttta caaacatgaa 8040
caactcctcc tgtaaccttc tgcaagtgtt taagatcgac gacgcatctc gcgatgtcag 8100
cgtcggtttc tatagcatcg ccatatgcgt cggactcata gcaaacatac tgatattact 8160
ggtcctaatc aaaaggcgaa aacttacctt tgccagcgac gtctactttc tgaatgctac 8220
cataggcgac atcgttacta ctgccacgct accgatatgg atgtattatg agctcywywv 8280
tsrnmkdvts rnmkkhgyhg ydwcvbatsr cdwcvbatsr nrmamhadat aragrahnta 8340
nttkwhnmar tndatnstat hcdcgtmsnw rmansymbar acrrnwhvvd ccdbasschc 8900
ksmwhnmart nwhnmartnh dtccdbassc hcksmccwhn martnnrmaw hnmartnmcr 8460
stwrdbddhc cddccdbass chcksmttdg dandaadaa" rtntryrtab wrddcmntsm 850
marynrmatn dcmntsmmar ynrmatncmb '"mcrstwrdd cmntmswrdd cwrddcmnt 8579
<210> 94
<211> 6675
<212> DNA
<213> Stealth virus
<900> 44
gaattcgtca tcatgacgtt cggggtttga tgttgccatg ttgactgacc tgcaggttct 60
gccgactgag ttccgttctg tgagtgtgtt tatttacatt caacatagat ggcgctaaac 120
agacaaacac agacatcaga aaacgttttt attacgggag tgaagagaca cagtggttac 180
agaccatggc aaacgtgacc ggtttctgcg ctgcctgttc tgcctccgga tcgggacgtg 240
acaggcgtat ggggaccagg tcctgcaggg cgatagaggc cccgaggagg gagagttggt 300
gcggcacctg gtgcaccgcc gacttcacct gatgcgccaa ggcggtgagc cgcccgcgat 360
tcagactgtg tttagaggaa atgaagtaga gctgtcccag tacggtgttt :.ttggtatgt 920
acgcgttctc gctcactacg ttaatttcta accaagtcct gggtagccag atggtgaccg 98u
gcatgttcag ttcttggcgg ttgtggggga taaagagtcc caggaagggt ccgtagaatc 540
ggcgatagat tcgaatgagg tgagacgttt tcagtgccaa gtcgtagggt aagcagacgt 600
cgaggccgcc . _ -gttgccgtcg tttcggggta aaaagtaagg gagcggcgtg tccgaaaaga 660
aaggacgcgc gacggtttgt cgccggaggc gcagtcgaaa cgacacgacg ggattggatg 7~~~
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27744
ggagttggtg ttgtgcgctg cggaaggtta cgttgaatcg taggatcccg tcctgataca 780
gaatcaagga tgatagcacc aaatccggag acccgtcgtc tacgtagagc tgcccgaaga 840
tggctggtcc catgttctcg atcgtacttt ctgagagttt cacggagatg cggctggcaa 900
ggccgcgcgg tcccgagatt ccgccctctg cggtgtgcca gcagagggcg gacttgaccg 960
ggatcatcag ctcgggcgtg ttgttgcttt cgtcggtcgt gaaagttagg tccggcatat 1020
gaagcgatac gcagtcgtgt agtgttgtgt ggtgagtgac ttttcgtcgc agaggtagct 1080
ggtgtctcag gggcggcata gttttgaggg cgaagatgtt tagcgacagt ctcacgatgg 1190
acatatgggt cagctgttcg tcaataacgg ctcgaagaat attgcaacta ccggcctgtg 1200
cggagaaaag ggcggcgatg ggtaaaatgt ccgagtcgcc attggctgcg gcgcacagga 1260
ggcctcgctc ttcggggtcg cggtgcgggg tgatcggctc gagctgcagc ggggtggaga 1320
gcaagatctg gaacggatgc tctaggtcgg tcggttgaaa gtctacgttc agctggatga 1380
gacgaaacgt gccctcgcgc gtcaggggtc gcttgacgtg gtgctggtcc gtcagggtta 1440
agatggtctc gtcagattgc aggagatttg aggcctttcg ggggcggcct cgaggcccat 1500
tccgcaaggt tttgtcggct cgcggcatgg tttgagactg atctccgcag cggggcggct 1560
cagcctttaa atatgcaggt cgcggatttg ttatcgggtg aaacgtcaca gaccgtaaac 1620
attacctgtt cgttgatgag atcatcgagc tgccttagca taacaaacaa agccgagagc 1690
cgagaaattt cttcgtccgg cgacacgtgg ttggggcgcc cgcggggccc atcggcgtgc 1740
tcgcggtcca gccgcatcaa gagttcctga cactttacca gtagcatgga gctgtcttcc 1800
agtgccaatt tacgcacgta gttcatcgtc aagtcggaag ccaggttggc taccatggac 1860
attgagaggc acgcggtttt catgtccagg aggaggtggt tttcgatcac gggatcggga 1920
atcgtgaagg tggcgtcgcg aaacgtaacg tgttgtagtt gattgacagc agctttaact 1980
tcttcgtaag agcggtcgag cgaatacaga gccattatga ggatcctctg gttgatctct 2040
acagccagtt gcgagggtaa cagccatggg aggacgagat tccattgtcc cactgaaact 2100
ggatattccc gcaccaccgg accctgaaag agcgggggta gtaagcataa accgtcgcct 2160
ttttcccaga gaacgggccc ggtgttgagg acggtgtaaa gctgtccgtg ggtgggaact 2220
tgcatagcga gttggttgcc ctcgattcgc cgcagaatcg tcggcgtcat gttgcgaagc 2280
agacttcgga gtcgaacata gccgcgcgtg ctgtcaatgt attggtgcaa acccaggtgg 2390
tggtgtttga tgaggtggtg tcggctgggg acggggatga tggctcccgt gagcttagcg 2900
agtttaccca cgtccgtgag gctgagtttt tgctcgaagg tgcagaaaat ggagaagtcc 2460
atggtgccac cggttcttcc agctctaact agcgtgctcc gtcaaatagt cagaggcaat 2520
ctttacgagt taaataacat gtgctgatgc aacgggatga tttcgcctat cacgtagttg 2580
ccgaagtgag tttccgacgt ggcgagcgat ccggacggat tcttgagctt gctttccata 2640
agagcctgcg tcgtggtgga aaggatgggc aaggcctctt gcagcatgcg acagggattc 2700
tcgattaact gttccgttcc ctcgacgcag atgtattggg tgtcggtttc cccgcgaata 2760
cagtctttgg ccctaaggag atactcgtcg atggttttaa acaacgtttt gttggagtta 280
ataatgtctt ccgtgttaaa aaactgtgca caaggactgt agaattgcga attgtatccc 2880
agacgttcgc ggtttcgaat gttgtacagc atgtcaccta gggaaccccg gttggaggcc 2940
caagggttgc gtgtggaggc gaacgtttgg gcgtcggcct cggtatgatc gtacagagtt 3000
ttcatggccg cgtccgtgtc gtatggatcg acgcccaaca tgcaggaggt gcggccgcgc 3060
gggttgttag ggattttgaa ataattaatg tctgtagtga cgggtgtaat gatgatttcg 3120
catatggctt tctgtccgtg caggtttgcc gcggagtttt tctctgacat gctaccgaaa 3180
gttaacatag agatagcctc ggtgtccaag agctgcggac ggtcgacgcc agcggcgtga 3240
cggacccacc gatcaacatc gtcgtgtcga tggacgtgca tggggaagac gcggaagaag 3300
ttctgcacgc gcacgcccac gtcgctgcgc gatcggttta ggtacgcgat gcaggtggtc 3300
gaggtgtaac ccagacccat gtccacgctg ttaatgttct gtgtcacgtg atacgtcgta 3420
ttgatgtccc gctcttcttt agtgacctga ggattattga tgataagtga cgcgcaggac 3930
ttgccgctgt acagcagcat gtcgacctcg aaagtgtcgg tccgtacggc tgtcagagcg 3540
aaaccggggt gaactccggc tttggccatt agtgcaatgg agacgggaga tattttgtac 3600
56
tcgcgcacga tatttttttc atgaacatga tgttcacgga cctggc
CA 02282858 1999-08-24
WO 99/34019 PCT/US98/27?44
atcatacagg ctaaggttaa cacagattgt agggtgttgg gacatcccgc tgtgtagcgt 3660
gagaaggggg agcggagcca gttccagtat tcgtgtgcca gagcggtggc cagcgggaaa 3720
ccgccgtcgt ggcgatggta gtgaggaaag tcggtgatgt atcgcttgat gtcgtcgttg 3780
atggctgcgc agatggtggg atcggagtag aagcggtgga aggggatcac gaaacagtat 3840
tctgccatga ttttgggagg tgttacggcg cagcatccgt tgtacaggac gtgttgcagg 3900
gacgtaaaat ctggcgtacc gtggcgctgg gccgggtcca gctgtgcgcg cacttccaaa 3960
attttggcgt gttcgggcac gaactggagg acgaggaaga gttctcggca ggcctcgtac 4020
aggttaacgt cttcgctggt accaatgtct tctaccatct gcgtcagcat ctctccgata 4080
gcttcgggtt cgttgggcat ggtgaaagcg gggcggtaga acaggtccac caacagagtc 4140
ttcagattca gaccgatccc acaggcccgg ttgttcgtca tagctggcat aaggcacagg 9200
tagaaaatct tctgcagcgt ccactcgtcg tcggtagctc ggtggtcgtc gacgaacagg 9260
ggttcgtcgg cgtccatagc cgccatgcgc gggacgtccg acacgccatg atgtcgggac 4320
tcgatattgg cgttgttgag gggttggcgg tcggcgacga tatggacgcc ttcttggttc 9380
cggggtaagt gagttacgaa aggcggccac agacggtgat cgtggagcgc gttggcatag 4490
gcggctagag gttcgtctac caggtgcccg ttgttgagtc ctgggagcga agaaacgcgg 4500
gtgacgagtc gcaggagggc catgatggtg cgataatgcg cgtggatgtt ggcgggcagg 4560
aggccgtcgc caaggtgctc gacgatcata gcgatcatgc tgtagctgtg gctgaaagcc 9620
aaaagttggc gattctgaaa agcgttgacg atacatcggg cgataaacgc gcggatgacc 4680
aagaaggcgt cggaattgcc gtggaccagc aggtccacca ggtagaagac ttcggggtag 9790
ttgggacagg acagggtgct ttttaacaat tgcagggtgg cctcgtagtc cggaggtggt 9800
cggagtcgga ccatctcggc gatgtgtgat gtacgtagtt cctgaaagga gctgggggct 4860
agtgcgtcag gaatgttgcc aatcacaatg cgcggggtgc agagggtgga ggtctccccg 4920
ttctcttggt ggtgcgtgag gtcgaagaaa gggtggagtt cggtgtacag ggttaagttt 4980
cctatcttgt aaaaatcatt ggttgtgtag tcctgcttga tctcgttgac cgtgcgcgga 5040
acttctcggc gtacgcggta gaagtgggtg aggcgcctgg cgataccggc catctgttct 5100
tgttggaagc gacattcggt gagtcgggct acggccgggt cggtgggaac gcctctatcc 5160
gtaaagacct gtaggcacgg tgcggattcg tacatgaccg ggtggcacaa ggttgccaac 5220
gcatcaataa agtcgagtcg ctccagaccg cggtcgcggt tcaagaggta agcggaggtg 5280
gggagcgcgt tttctttggt ttcggccagt ttcaccttgt tctccactgt ggtgtaggct 5340
cgatcttccg ggagatagag acccactgga aagaaaaagg tgagatcgat gtttctttcc 5400
aaggggtctt tggtgtcggt gtttttgtac actcgccgct ggtgctctag ggccacggcg 5960
tgttcgccaa gttggataac gtccatggat agcgaggtga gactgttctg tccggctttt 5520
tccagagagg agccggtgag atcggggtta cccgaggtca ggtgagcggt ataagagtta 5580
aagtcggcca ggatagaatg gtgagcgatg gctgtgacgg cgttttcggg gctgagtaca 5640
aaattgccgt aggtggccgg ggcggagaca ttttgtttgc tgatactgct tttcaggagc 5700
gtcatgagag tttgaacgac ctgagcggtg ctgactatca cgccccggag ctgcttgccg 5760
gagcctgtca cgtacgtgct ggggttttct aggatactgt tggtggtggc ttccaccatt 5820
tttgtgagca gcttcgagat gtagtcgcga tccgacgtgc ggttaagcag aaacatggtg 5880
ctgagcattt ttgttttgaa actctgcagg atgttgcttc gttggatgcg gttcagggct 5940
tgacggcaca acgtggcgtt ttcgaccagc gtctgcacca cgaagtaagg cggggcttta 6000
cgcaacagta cctggagaaa gcagtggatt aagcctcgct ccatggcgtc ggcggtgttt 6060
ttcaacgcac gcagcacggt gtgcatggct tcgacattaa ggatcttgtc gaggatggtg 610
ttctcgaacg tttctcgcag gtgcgtgaga caggcggcgc tgagctcgaa ggggatggtg 6180
atggggcttt tttcactgta tttggtaacc atgatggtgg tctgtctcga ggtgggcatt 6240
ccggcgccgc tggctacacg cggcacctgg atgtgaaaca gcattttccc tgttgtcatc 6300
ttgttcaggt catcgaactt gatggcgtgc gcggccgatg ccagggccgt ctggaggaag 6300
taaacccatt cgagacgatt gcagaaggtg ccgaagatgg cttcgaagtg gatgttgtag 690
cgttccgggt catctccgta gtaaatgcgc agactgtcga acatttcttc cccggcgctg 6980
57
*rB
CA 02282858 1999-08-24
WO 99/34019 PCTlUS98/27744
gtttttacat gcgtgagaaa gtcggccggg atcccgactt tcgggagtaa ctcgactgcc 6540
gtccagtttt ccatgacggc gtgcggcgat ggcttcctcg ccaaccgtct ttcagtgtcg 6600
cgcgccccag gacgctctaa tagtggagtc ggcggcggaa ccccaggtcg tcaatgtccc 6660
cgtacacgtg aattc 6675
58
*rB
