Department of Medical Physics, Royal Perth Hospital, Western Australia, 6001,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso, Sam Mhlongo, Todd Miller, Christian Fiala
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The non-existent knobs on "HIV" particles
In his rapid response "Re: Re: Re: Show me the photo please:, 24th June, Christopher Noble wrote: "The Perth Group invented these rules ["for retrovirus isolation"] only after it became clear that HIV exists and causes AIDS and that their pet oxidative stress theory of AIDS was untenable".
We have repeatedly told Christopher Noble we did not invent any rules for retrovirus isolation. However, his persistent questioning leads us to ask what exactly is Christopher Noble’s problem with “rules”? Does he believe retroviruses can be proven to exist without adhering to any “rules”? Or does he think only certain people are permitted to lay down the “rules”? We accept that Christopher Noble knows all about the properties of retroviruses. So what is the big deal about his coming up with a set of procedures which by which the existence of a new retrovirus can be proven? If he cannot manage that why can’t he post a method that belongs to someone else that satisfies him and achieves the same outcome? Then at least we would have something to discuss and debate.
Christopher Noble does not mention why the oxidative stress theory, most of whose predictions have been fulfilled,1 is untenable. However, it may prove educational to read what the "discoverer" of "HIV" has to say. As mentioned elsewhere in this debate, if one reads Montagnier's latest writings2 and interviews3 one would be excused for concluding that Montagnier is an apologist for the oxidative and not the "HIV" theory of AIDS. More than a decade after the oxidative theory of AIDS and "HIV" was proposed, Montagnier wrote:
"A large body of data on in vitro human immunodeficiency virus (HIV) infection and biochemical clinical studies suggests that oxidative stress plays a role in AIDS pathogenesis. Recent reports have implicated intracellular excess of reactive oxygen species (ROS) in the induction of HIV expression and in the initiation of apoptotic cell death. Studies showing a decrease in glutathione in peripheral blood mononuclear cells from symptom-free persons offer further evidence of a metabolic alteration leading to the decreased ability to counteract oxidative stress…In AIDS pathogenesis, oxidative stress is proposed as a metabolic alteration that favours disease progression by inducing both viral replication and apoptotic death...Indeed, evidence that oxidative stress induces, while antioxidants inhibit, HIV replication and apoptosis suggests the use of these molecules as an antiretroviral therapy to reduce cell death in AIDS patients"446 (italics ours). However Montagnier does not indicate what difference exists between his proposal of the role oxidation plays and our oxidative theory of AIDS and "HIV". Most importantly, he does not indicate what is the cause(s) of the oxidation in these patients nor does he comment on the causes we have been proposing.
In his book Virus, under the heading “Oxidative Stress”, Luc Montagnier wrote:
“What happens in patients suffering from AIDS? One notes a significant shortage of antioxidants and a rise in oxidation products: the level of glutathione in the lymphocytes decreases, peroxidised lipids appear in the blood, proteins are also oxidized, and for this reason undergo very rapid enzymatic breakdown. The phenomenon is massive, and occurs at an early stage…We know that the products of this stress can trigger cellular apoptosis…Aside from a small number of pioneers-Droge in Germany and Leonard and Lena Herzenberg in the United States-very few researchers have shown interest in this phenomenon, despite its fundamental role in the illness". (emphasis ours)
Again he does not indicate what is the cause(s) of the oxidation, nor does he comment on the causes we have been proposing.
NOTE: The oxidative theory of AIDS was proposed at the beginning of the AIDS era. In 1986 a paper arguing this hypothesis was twice rejected by a leading scientific journal and appeared in Medical Hypotheses in 1988. Since then we have discussed our theory in several other publications including in 1992, in the Pasteur Institute publication Research in Immunology, where we wrote: "As long ago as 1983, one of us (EP-E) proposed that oxidative mechanisms are of critical significance in the genesis of AIDS (acquired immune deficiency syndrome). A prediction of this hypothesis was that the mechanisms responsible for AIDS could be reversed by the administration of reducing agents, especially those containing sulphydryl groups (SH groups). The discovery of HIV resulted in a broadening of this hypothesis in that it considered oxidative stress as a principal mechanism in both the development of AIDS and expression of HIV…All this argues in favour of oxidation as being a critical factor in the pathogenesis of AIDS and HIV expression".
In 1992 one of us made Luc Montagnier personally aware of our oxidative theory and sent him our published papers on this topic.
Would Christopher Noble please tell us why he finds our "pet theory untenable"?
Christopher Noble wrote: "If you think there are no EMs of HIV showing spikes you have been deceived by the Perth Group. Early work by Hans Gelderblom shows nice EMs of HIV showing spikes and cone shaped central core. (3) If you can't tell the difference between this and microvesicles then you need to get your eyes checked.
If you want something more recent look at this paper by Zhu et al (4). It shows nice 3D tomograms of sucrose gradient-purified preparations of SIV and HIV-1 virion where you can clearly see the spikes and can even resolve the trimer structure."
In one of his 1987 publications Hans Gelderblom reported that knobs are found only in the budding (immature) particles and not in cell free (mature particles); immature particles are very rarely observed.4
In Christopher Noble's ref. 3 Hans Gelderblom and his colleagues paid "special attention to morphology and number of virus envelope projections". They reported: "While most of the mature particles lacked a uniform fringe partially or completely, these projections are especially evident around immature and/or budding particles, where they form an equidistant pattern. During "maturation", virus particles loose their knobs progressively. This loss seems to be rapid and becomes particularly evident when parallel cultures harvested at different times were compared…Shedding of envelope proteins is a common phenomenon of retroviruses. The extent and velocity of loss of surface proteins in case of HIV, however, appears extraordinary…The loss of surface knobs apparently correlates morphologically with virus maturation. Immature and/or budding HIV particles are "spiked," but they are rarely observed."
In a 1993 publication Hans Gelderblom and his colleagues have estimated that immediately after being released from the cell membrane "HIV particles" possess an average of 0.5 knobs per particles which are rapidly lost, but also pointed out that "it was possible that structures resembling knobs might be observed even when there was no gp120 [knobs] present, i.e. false positives."
The picture in Zhu et al's paper entitled: "Electron tomography analysis of envelope glycoprotein trimers on HIV and Simian immunological virus virions":
(i) shows only one particle (most probably the best result they could obtain);
(ii) it is not an electron micrograph of an HIV particle but a tomogram reconstructed from multiple EM images of the same virion;
(iii) unlike the "tomogram sections from a SIVmac239", the reconstructed surface of the "HIV" tomogram is far from convincing.
Discussing their finding Zhu et al wrote: "Although wide spacing of limited numbers of trimers seems difficult to reconcile with models that postulate a requirement for co-operative binding of multiple trimers to mediate infection, the low particle infectivity ratio of retroviruses, including HIV-1, leaves open the possibility that a small fraction of virions, potentially with much higher env content per particle or those bearing stochastically or structurally fostered microclusters of env, might be responsible for most or all of the infectivity in virus preparations. Depending on their frequency, particles with high env content, if present, might not have been sampled in the analyses reported here". In other words the number of knobs, if indeed there are any at all present on the particles, are not reconcilable with the generally accepted view of HIV infectivity.
1. Papadopulos-Eleopulos E. Looking back on the oxidative stress theory of AIDS. Continuum 1998;5:30-35. LINK
2. Montagnier L, Olivier R, Pasquier C, editors. Oxidative stress in cancer, AIDS and neurogenerative diseases. New York: Marcel Dekker Inc, 1998.
3. Passwater RA. Antioxidant Nutrients and AIDS: Exploring the Possibilities--An interview with Dr. Luc Montagnier, the discoverer of HIV. Whole Food Magazine, 1995:50-65. LINK
4. Hausmann EHS, Gelderblom HR, Clapham PR, Pauli G, Weiss RA. Detection of HIV envelope specific antibodies by immunoelectron microscopy and correlation with antibody titer and virus neutralizing activity. J Virol Meth 1987;16:125-137.
Competing interests: None declared