A refutation to some of Duesberg's Stuff

Prof Peter Duesberg is a retrovirologist who did some of the best work on Rous Sarcoma Virus. He mapped the src oncogene, a piece of work that was incredible considering the lack of molecular techniques available at the time.

However, he applies his understanding of simple retroviruses to HIV, a complex retrovirus (complex because it contains accessory genes) and concludes that HIV cannot cause AIDS. Moreover, he goes onto say that drug use causes AIDS.

Here is my personel rebuttal to Duesberg's anti-HIV argument.


Pharmac. & Ther. Vol. 55: 201-277, 1992
AIDS ACQUIRED BY DRUG CONSUMPTION AND OTHER NONCONTAGIOUS RISK FACTORS
PETER H. DUESBERG


3. Discrepancies Between AIDS and Infectious Disease

3.1.Criteria of Infectious and Noninfectious Disease

Based on common characteristics of all orthodox infectious diseases, infectious AIDS would be predicted to:

(1) Spread randomly between the sexes. This is just as true for venereal as for other infectious diseases (Judson et al., 1980; Haverkos, 1990).

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Except a new infectious agent that spread into the Western world (which, lets face it, is all Duesberg is talking about) through the homosexual population. Spread to women and heterosexual men would be expected (and was observed) to be slow and incomplete.

HIV spread is equal among the sexes in the heterosexual epidemic in Africa.

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(2) Cause primary disease within weeks or months after infection, because infectious agents multiply exponentially in susceptible hosts until stopped by immunity. They are self-replicating, and thus fast acting toxins. (Although "slow" viruses are thought to be pathogenic long after neutralization by antiviral immunity (Evans, 1989c), slow pathogenicity by a neutralized virus has never been experimentally proven (Section 6.1).)

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HIV causes an acute seroconversion illness in about 50% of those it infects. This is like most other viral illnesses, since the symptoms are not caused by the virus but instead by the release of cytokines such as IL-2 and the Interferons, which produce constitutional unwellness.

Also he is assuming that the presence of antibodies to HIV means that they are _neutralising_ antibodies, and yet he makes no effort to prove this. The fact that HIV can be detected even after an antibody response might argue against this, but doesn't take into account direct cell-to-cell spread. Many viruses persist despite antibody recognition, and antibodies do not have to be neutralising, some are in fact pathogenic. (Mitler and Hoffmann: Science 1989) Examples are HSV, EBV, VZV, Hep B. The herpes family maintain their genome in host cells, and their latency is less well understood than that of HIV. At least we know that T cell activation results in HIV expression (the same transcription factors, such as NF Kappa B are used) while for the herpes viruses we don't even have that handle. Hep B is a reversivirus, related to the retroviruses by its use of reverse transcriptase. It doesn't integate into the genome. However, it's persistance is also a mystery - there is a vigourous immune response, which results in the liver destruction which gives this virus its name (the virus is not in fact cytotoxic to liver cells). It also produces massive quantities of non-infectious particles, so much so that the viral particles have a special name (Dane particles) to distinguish them from the rest of the junk found in the serum. These may act as decoys for the virus against the immune response (ref for most of the above: Fields Virology, or any other virology textbook - Duesberg should have known all this).

Also, it is known that CD4 counts plummet during this acute stage, from ~1000 to ~500 (the lower end of normal) before picking up again as HIV-specifc immunity appears (Pantaleo et al: NEJM 1993 review). While these levels are not going to result in opportunistic infections appearing, they are a definite sign of things to come.

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(3) Coincide with a common, active and abundant microbe in all cases of the same disease. (Inactive microbes or microbes at low concentrations are harmless passengers, e.g. lysogenic bacteriophages, endogenous and latent retroviruses (Weiss et al., 1985), latent herpes virus or latent ubiquitous Pneumocystis and Candida infections (Freeman, 1979; Pifer, 1984; Williford Pifer et al., 1988). Hibernation is a proven microbial strategy of survival, which allows indefinite coexistence with the host without pathogenicity.)

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There is evidence of HIV virus particles in 100% of AIDS cases and over 99% of those with anti-HIV antibodies (Jackson et al: J Clinical Molecular Biology 1988 and 1990). The low level of HIV in the plasma of infected people (often to uncultureable, though not undetectable levels) after the first week/fortnight (Piatak: Science 1993, Pantaleo et al: NEJM 1993 review) suggests that the immune system is actively hindering HIV replication, especially since antibody titres to HIV go up reciprocally. As for abundant microbe - tetanus toxin from clostridium tetani bacteria can and does kill in quantities too low to mount an immune response to. This also feeds into the following claim...

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(4) Coincides with a microbe that lyses or renders nonfunctional more cells than the host can spare or regenerate.

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And/Or hinders the regeneration of those cells. HIV reduces the CD4 cell survival time and hinders replacement from the thymus. The effect of HIV is reversed by antiviral therapies. (Duoek el al: Nature 1998, Hellerstein et al Nature 1999) HIV is cytotoxic (Yelle et al: Archives of Virology 1994, Rasheed et al: Virology 1996, ), and may be immunosuppressive even in the absence of active infection (Diamond et al: J immunology 1988, Weinhold et a l: J immunology 1989, Daniel et al: Clinical Experimental Immunology 1993, Liegler and Stites: J AIDS 1994, Theodore et al: J AIDS 1994, Schols and De Clercq: J Virol 1996, etc - I haven't even started on the accessory proteins of HIV). The immune response to the virus will, of course, attack the immune system itself. As such the number of cells the virus actually kills by infection need not be the limit of the immune dysregulation. Direct in vivo evidence of this lack of correlation between cytotoxicity and immune suppression exists in chimps (Wantanabe et al: J Virology 1991).

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(5) Generate a predictable pattern of symptoms.

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Longitudinal studies shown that after ~15 years 90% of those with HIV infection with progress to a stage of gradual immune decline, with increased risk of opportunistic infections, a specific supression of cytotoxic immune responses with (usually) a simutaneous rise in antibodies.

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Duesberg also moans that HIV cannot possibly be neurotoxic and a cause of AIDS dementia, since the retroviruses he worked on didn't infect non-dividing cells. He seems to ignore the fact that HIV does infect the non-dividing T cells, an ability later ascribed to the vpr protein found
in HIV, but not in the simple defective retroviruses he worked on. He also doesn't know that HIV's neurotoxicity is due to infection of the CD4+ astrocytes in the brain, and subsequent loss of neuronal support leading to cell death. Again - a non-direct method of disease.


There is plenty more of course, but based on this logic the argument that HIV cannot be the cause of AIDS seems untenable to me.