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Stealth Viruses and HIV: A Potential Role in the Emergence of the AIDS Epidemic
W. John Martin, M.D., Ph.D.
She was HIV negative, yet he was seropositive. She became the focus of studies on stealth-adapted viruses; he went on to die soon from AIDS. They had not been intimate, but were good friends. They were experiencing similar symptoms including headaches, difficulties with clearly expressing themselves, altered sleep pattern and activity-provoked extended fatigue. They both tested positive in a culture for stealth-adapted viruses.
What did this mean? A positive HIV test will typically preclude further inquiry why someone’s brain may not be fully functional. Even overt dementia is all too readily attributed to HIV, especially since partial clinical recovery can follow anti-retroviral therapy. An alternative suggestion is that HIV is not the complete answer, but that stealth-adapted viruses are co-factors not only in the clinical manifestation of HIV infection, but also in disease progression.
Various grant applications to pursue such an idea aroused little interest among Government or private sponsored granting agencies. The concept of stealth-adapted viruses was itself considered too far fetched, let alone trying to link these viruses to AIDS. Even clinicians being told that their HIV infected patients were testing positive in a stealth-virus assay, were left wondering where to go next.
The forthcoming publication "Chemokine receptor-related genetic sequences in an African green monkey simian cytomegalovirus-derived stealth virus" Exp. Mol. Path. (in press), extends some of the concepts developed by those studying the potential role of human cytomegalovirus (HCMV) and of human herpesvirus-8 (HHV-8) in AIDS. Interest in HCMV stemmed from the finding that HIV utilizes CC chemokine receptors in cell attachment and intercellular penetration. HIV infection is inhibited if the receptors are occupied by CC chemokines such as RANTES. The US28 gene of HCMV codes a molecule that shares functional homology to the CC chemokine receptor. HCMV can potentially facilitate HIV spread by: i) Providing actual receptors for HIV entry into cells; or ii) absorbing chemokines, such as RANTES, from the local environment, thereby freeing up other receptors for HIV attachment.
The prototype African green monkey simian cytomegalovirus (SCMV)-derived stealth virus, isolated from the female patient mentioned at the beginning of this article, has not one, but at least five copies of a US28 related gene. Also, unlike conventional HCMV, the stealth-adapted virus can express itself without evoking an anti-viral cellular immune response. It was detectable within the cerebrospinal fluid (CSF) of the patient, and was able to induce brain disease when inoculated into cats. It seems implausible that such a virus could not influence the pathogenicity of HIV.
Chemokine receptor expression by stealth-adapted viruses also parallels current thinking as to how HHV-8 may cause Kaposi’s sarcoma. Like HCMV, HHV-8 also codes for chemokine receptors. Outgrowth of seemingly malignant cells in Kaposi’s sarcoma is attributed in part to their being driven to proliferation through the viral coded chemokine receptor. Whatever mischief a conventional HHV-8 virus might cause, a stealth-adapted HHV-8 is likely to do more.
If stealth-adapted viruses are contributing to the neurological illnesses experienced by HIV infected patients, why do the patients respond to anti-retroviral therapy. There are now good indications that some stealth viruses use reverse transcription in their replication process. Stealth virus activity could easily be monitored in HIV infected patients following the institution of anti-retroviral therapies.
A nagging question is whether stealth-adapted viruses were relevant to the emergence of AIDS as an HIV associated illness. Much has been made of the possibility of HIV being transmitted to Africa through contaminated polio vaccines. It may be the vaccines’s stealth-adapted viruses that promoted the growth of what was essentially non, or poorly pathogenic, primate retroviruses. Or possibly, both a retrovirus and a stealth-adapted virus were inadvertently transmitted to monkeys. It is particularly noteworthy that simian immunodeficiency virus (SIV) infection is not universal among many African green monkeys. Moreover, monkeys transported from Africa early in the 20th century were not infected. Data indicating continuing re-assortments and mutations of the HIV-related retroviral genomes in primates are also consistent with a relatively recent origin and is in contrast to the relative stability of non-pathogenic spuma retroviruses.
In summary, stealth-adapted viruses have not uncommonly been cultured from HIV-infected patiets. They can potentially cause neurological symptoms inappropriately attributed to HIV. Stealth viruses can also potentially exacerbate HIV, and may have been responsible for the emergence of the AIDS epidemic. A search for stealth viruses within African primates should be undertaken.
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