Presented at
International Conference on Emerging Infectious Diseases
Centers for Disease Control
March 26, 2002
W. J. Martin MD PhD
Center for Complex Infectious Diseases
Stealth Adapted Viruses
Abstract
Stealth-adaptation
is a mechanism that allows cytopathic viruses to evade immune elimination
through the deletion of genes coding the major antigens targeted by the
cellular immune system. A prototype stealth-adapted virus, repeatedly cultured
from a patient with chronic fatigue syndrome (CFS) was cloned and partially
sequenced. It has a fragmented, genetically unstable, genome. It has retained
numerous viral sequences that can be aligned to various regions of the genome
of human cytomegalovirus (HCMV).
Where the
comparison can be made, the sequences match much more closely to those of
African green monkey simian cytomegalovirus (SCMV) indicating an unequivocal
origin from SCMV. Kidney cells from cytomegalovirus seropositive African green
monkeys were, until recently, routinely used to produce live poliovirus
vaccine. The SCMV-derived stealth-adapted virus has five adjacent, but
divergent, open reading frames that potentially code for molecules related to
the US28 CC chemokine receptor protein of HCMV.
In addition,
the virus has acquired cellular sequences from infected cells, including a set
of three divergent genes that potentially code for proteins related to the
putative oncogenic CXC chemokine known as melanoma growth stimulatory activity
(MGSA/Gro-alpha). The genes in the prototype SCMV-derived stealth-adapted
virus, supports current experimental therapeutic approaches based on chemokine
suppression. Interestingly, the MGSA-related genes generally lack introns and
were, therefore, presumably assimilated into viral DNA from cellular RNA
through reverse transcription. The virus has also acquired genetic sequences
from various bacteria. This finding has led to the secondary designation of
this type of novel microorganism as viteria.
Molecularly
heterogeneous viruses, inducing similar cytopathic effects in culture (and when
examined, non-inflammatory vacuolating cellular damage in brain and tissue
biopsies), have been cultured from numerous patients with severe neurological,
psychiatric, immunological and neoplastic diseases. In controlled, blinded,
studies, cytopathic effects were recorded in 9% of healthy individuals donating
blood for transfusion; in contrast to the positive results recorded in
virtually all blood samples from patients with various illnesses. The differing
clinical manifestations in infected patients may reflect the assimilation of
different cellular and other sequences in various stealth-adapted viruses. Stealth–adapted viruses (and viteria) pose a
major threat to Public Health.
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Background Information
A. There is an increasing incidence of diseases with accompanying
signs and symptoms of brain damage. These include neurological and psychiatric
illnesses, childhood behavioral disorders, and such common conditions as
chronic fatigue, Gulf War Syndrome, so-called "chronic Lyme disease",
and many cancers. Altogether, these diseases have an enormous social impact.
B. An infectious cause of many of these chronic illnesses has not
been considered primarily because there is no inflammation in the involved
tissues.
C. Brain biopsies do, however, show cells with damaged
mitochondria, lipid vacuoles, and irregular inclusions. Examples are shown in
the figures 1-5.
D. Viral cultures from patients with neuropsychiatric and other
illnesses, regularly develop clusters of foamy vacuolated cells. These cellular
changes are consistent with infection by actively cytopathic viruses. Figures
6-7.
E. The cultures are also remarkable in the production of large
quantities of lipids, including cholesterol esters, and pigmented,
protease-resistant, aggregates and ribbon-shaped materials, some of which
incorporate metals. Figures 8-15.
F. Viral cultures can induce severe, non-inflammatory, widespread
illness when inoculated into cats. The cytopathic effect (CPE) seen in tissues
of infected animals is comparable to that seen in the tissue cultures.
G. While the viruses causing CPE in viral cultures differ in
different patients, one viral isolate was unequivocally derived from an African
green monkey simian cytomegalovirus (SCMV). The issue of probable SCMV
contamination of live polio virus vaccines produced in kidney cells of African
green monkeys was identified by Industry and FDA in 1972. Unfortunately, this
potential problem with live polio virus vaccines was not publicly disclosed,
nor scientifically addressed.
H. Continued sequencing of DNA isolated from this cultured virus
shows intriguing genetic modifications. Apparent loss of critical viral genes
can explain how the virus evades the cellular immune system. Sequencing also
reveals the surprising presence of an assortment of bacterial genes, including
genes very closely related to those of Brucella, Mycoplasma, Streptococcus, and
other bacterial species. This finding shows the capacity of such viruses to
pass, and possibly, to have been passed, through bacteria. Stealth viruses can
also potentially incorporate cancer causing cellular genes, as shown by the
presence of a cancer-related chemokine gene in the SCMV-derived stealth-adapted
virus.
Methods and Brief Summary of Sequencing Study
DNA isolated
from the stealth virus culture was cloned and sequenced. Nucleotide sequences were analyzed using
Blast Programs at NCBI.
While the
complete genome of human (HCMV) is known, only partial sequence data are
available for African green monkey (SCMV), Baboon (BaCMV) and rhesus monkey
(RhCMV) cytomegaloviruses.
Most of the
clones aligned to CMV sequences. Near identity of some clones to SCMV.
Several clones
contained atypical sequences of bacterial origin.
Other clones
partially matched to human proteins, including to a cancer associated
chemokine, and to various highly reiterated genes present in the human
genome.
The sequence
data clearly establish the existence of atypically structured viruses.
Conclusions
Atypically
structured, non-inflammation inducing cytopathic viruses definitely exist.
Some of these
viruses were derived from simian CMV and have presumably entered the human
population from SCMV contaminated batches of live polio vaccines.
Non-inflammatory
cytopathic viruses are grouped under the term "stealth." They
can be regularly cultured from patients
with complex multi-system illnesses, including
various cancers. Positive stealth virus cultures were found in
approximately 10% of University students donating blood for transfusion.
Community outbreaks do occur.
Stealth-adaptation
is considered to be a generic process that can involve many types of cytopathic
viruses. It presumably occurs through the loss of genes coding for major
antigens normally targeted by the cellular immune system.
Tissue culture
provides the best method to screen for stealth-adapted viruses. Viral cultures can also provide useful
insights into pathology, including formation of lipids, and of
protease-resistant protein complexes.
The production
of lipids and pigmented materials is viewed as a reparative process helping to maintain cell viability.
There is a marked reduction in the intensity of the CPE if the culture medium
is not frequently replaced.
Bacteria and
cell-derived genes are present in the SCMV-derived stealth virus culture. This
important finding indicates the potential intermixing of cellular, viral and
bacterial genes in the creation of new highly pathogenic organisms. Viteria is
used to define viruses with bacterial sequences. Atypical bacteria can commonly be cultured from stealth virus
infected patients.
Stealth viruses
are found in cancer patients, many of who have symptoms of an underlying
neuropsychiatric illness. The prospect of bacteria transmitting cancer causing
viruses is a very serious and urgent public health concern.
Bacterial genes
can help explain partial and inconsistent serological and/or PCR diagnostic
findings for mycoplasma, (in CFS, Gulf War Syndrome): Borrelia (in
"chronic Lyme disease"), streptococcus (in PANDAS), etc.
Apparent
expansion of chemokines and chemokines-receptor genes provide an adjunctive
approach to anti-stealth virus therapy. Many therapeutic agents are available
that can lead to cytokine/chemokine suppression.
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Additional information
including; 15 Micrographs, Sequencing data and references are available at
these links:
http://www.ccid.org/stealth/presentations/part2.htm
http://www.ccid.org/stealth/presentations/part3.htm
http://www.ccid.org/stealth/presentations/part4.htm
http://www.ccid.org/stealth/presentations/part5.htm
http://www.ccid.org/stealth/presentations/part6.htm
Further information is available on the
internet at www.ccid.org.
PUBLICATIONS
1. Martin WJ, Zeng
LC, Ahmed K, Roy M. Cytomegalovirus-related sequences in an atypical cytopathic
virus repeatedly isolated from a patient with the chronic fatigue syndrome. Am.
J. Path. 145: 441-452, 1994.
2. Martin WJ. Stealth
virus isolated from an autistic child. J. Aut. Dev. Dis. 25:223-224,1995
3. 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: 93-103, 1995.
4. Martin WJ, Glass
RT. Acute encephalopathy induced in cats with a stealth virus isolated from a
patient with chronic fatigue syndrome. Pathobiology 63: 115-118, 1995.
5. Gollard RP, Mayr
A, Rice DA, Martin WJ. Herpesvirus-related sequences in salivary gland tumors.
J. Exp. Clin. Can. Res. 15: 1-4, 1996.
6. Martin WJ. Genetic
instability and fragmentation of a stealth viral genome. Pathobiology 64:9-17,
1996.
7. Martin WJ. Severe
stealth virus encephalopathy following chronic fatigue syndrome-like illness:
Clinical and histopathological features. Pathobiology 64:1-8, 1996.
8. Martin WJ. Stealth
viral encephalopathy: Report of a fatal case complicated by cerebral
vasculitis. Pathobiology 64:59-63, 1996.
9. Martin WJ. Simian
cytomegalovirus-related stealth virus isolated from the cerebrospinal fluid of
a patient with bipolar psychosis and acute encephalopathy. Pathobiology
64:64-66, 1996.
10. Martin WJ,
Anderson D: Stealth virus epidemic in the Mohave Valley. Initial report of
viral isolation. Pathobiology 65:51-56, 1997.
11. Martin WJ.
Cellular sequences in stealth viruses. Patobiology 66:53-58, 1998.
12. Martin WJ.
Bacteria related sequences in a simian cytomegalovirus-derived stealth virus
culture. Exp Mol Path. 66: 8-14, 1999.
13. Martin WJ.
Stealth adaptation of an African green monkey simian cytomegalovirus. Exp Mol
Path. 66:3-7, 1999.
14. Martin WJ.
Melanoma Growth stimulatory activity (MGSA/GRO-alpha) chemokine genes
incorporated into an African green monkey simian cytomegalovirus (SCMV)-derived
stealth virus. Exp Mol Path. 66: 15-18,1999.
15. 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.
66:19-30 1999.
16. Martin WJ.
Chemokine receptor-related sequences in an African green monkey simian
cytomegalovirus (SCMV)-derived stealth virus. Exp Mol Path. 69: 10-16, 2000.
17. Martin WJ.
Stealth viruses. Explore 10: Number 4, 17-21, 2001.
18. Martin WJ.
Chronic fatigue syndrome among clinicians: A potential role of occupational
exposure to stealth viruses. Explore 10:
Number 5, 7-10, 2001
19. Martin WJ.
Chemokines and stealth viruses. A blueprint for therapy in infected humans and
animals. Explore 11, Number 1, 7-11, 2002.