Damned Heretics

Condemned by the established, but very often right

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Qualified outsiders and maverick insiders are often right about the need to replace received wisdom in science and society, as the history of the Nobel prize shows. This blog exists to back the best of them in their uphill assault on the massively entrenched edifice of resistance to and prejudice against reviewing, let alone revising, ruling ideas. In support of such qualified dissenters and courageous heretics we search for scientific paradigms and other established beliefs which may be maintained only by the power and politics of the status quo, comparing them with academic research and the published experimental and investigative record.

We especially defend and support the funding of honest, accomplished, independent minded and often heroic scientists, inventors and other original thinkers and their right to free speech and publication against the censorship, mudslinging, false arguments, ad hominem propaganda, overwhelming crowd prejudice and internal science politics of the paradigm wars of cancer, AIDS, evolution, global warming, cosmology, particle physics, macroeconomics, health and medicine, diet and nutrition.

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Many people would die rather than think – in fact, they do so. – Bertrand Russell.

Skepticism is dangerous. That’s exactly its function, in my view. It is the business of skepticism to be dangerous. And that’s why there is a great reluctance to teach it in schools. That’s why you don’t find a general fluency in skepticism in the media. On the other hand, how will we negotiate a very perilous future if we don’t have the elementary intellectual tools to ask searching questions of those nominally in charge, especially in a democracy? – Carl Sagan (The Burden of Skepticism, keynote address to CSICOP Annual Conference, Pasadena, April 3/4, 1982).

It is really important to underscore that everything we’re talking about tonight could be utter nonsense. – Brian Greene (NYU panel on Hidden Dimensions June 5 2010, World Science Festival)

I am Albert Einstein, and I heartily approve of this blog, insofar as it seems to believe both in science and the importance of intellectual imagination, uncompromised by out of date emotions such as the impulse toward conventional religious beliefs, national aggression as a part of patriotism, and so on.   As I once remarked, the further the spiritual evolution of mankind advances, the more certain it seems to me that the path to genuine religiosity does not lie through the fear of life, and the fear of death, and blind faith, but through striving after rational knowledge.   Certainly the application of the impulse toward blind faith in science whereby authority is treated as some kind of church is to be deplored.  As I have also said, the only thing ever interfered with my learning was my education. My name as you already perceive without a doubt is George Bernard Shaw, and I certainly approve of this blog, in that its guiding spirit appears to be blasphemous in regard to the High Church doctrines of science, and it flouts the censorship of the powers that be, and as I have famously remarked, all great truths begin as blasphemy, and the first duty of the truthteller is to fight censorship, and while I notice that its seriousness of purpose is often alleviated by a satirical irony which sometimes borders on the facetious, this is all to the good, for as I have also famously remarked, if you wish to be a dissenter, make certain that you frame your ideas in jest, otherwise they will seek to kill you.  My own method was always to take the utmost trouble to find the right thing to say, and then to say it with the utmost levity. (Photo by Alfred Eisenstaedt for Life magazine) One should as a rule respect public opinion in so far as is necessary to avoid starvation and to keep out of prison, but anything that goes beyond this is voluntary submission to an unnecessary tyranny, and is likely to interfere with happiness in all kinds of ways. – Bertrand Russell, Conquest of Happiness (1930) ch. 9

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John P. Moore Brings Down The AIDS Paradigm (Part 2)

Moore redeems himself by helping Duesberg destroy crux of HIV∫AIDS theory

Scores studies for ignoring obvious: HIV acts as vaccine against itself

John Moore, quiet Truthteller

samsonbigmaybe.jpgAs we were saying, the other day we made a remarkable discovery in the scientific literature of HIV∫AIDS.

John Moore, it turns out, has justified our obstinate faith in his exemplary character as a scientist in one of our most distinguished medical institutions by publishing a paper which finds the heart of the paradigm empty, and its claims of a virus overcoming the resistance of the body provably void.

Moore as paradigm assassin

To put it bluntly, John P. Moore Ph.D. has written a paper which tears out the thumping heart of his entire campaign in defense of the beleaguered paradigm and throws it to the paradigm attack dogs he is usually occupied with trying to kick as hard as he possibly can.

The title of this quietly seminal work is a question: “Is there enough gp120 in the body fluids of HIV-1 infected individuals to have biologically significant effects?”

The minireview can be found in Virology, 323 (2004) pp1-8, and is written with P. J. Klasse, who is also at the Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, W-805, New York NY 10021 (Fax 212 746 8340 jpm2003@med.cornell.edu).

Gp120 is the envelope glycoprotein of the vaunted Human Immunodeficiency Virus, which Moore in public is strenuous in insisting is the valid root cause of the statistically burgeoning AIDS pandemic reported by the New York Times and the Council of Foreign Relations and other very established sources of public advice to be spreading around the world and threatening the security of almost every nation.

Private science

Apparently he is not saying the same thing off stage, however. It seems the paper was a review more or less intended for the private reading of the HIV virologist’s club, and not for the general public or even the edification of journalists and science writers.

This double think is standard behavior for the well funded members of the HIV∫AIDS elite. They profess one thing in public, and like to carry on their real discussion behind the scenes, talking more realistically among themselves about their stock in trade, the belief that HIV somehow causes AIDS, and wondering aloud how it could possibly be reconciled with the stream of contradictory studies pouring forth very year, without unsympathetic interlopers present who might notice the dissonance between public confidence and private admissions about the missing heart of the paradigm.

Secretly supporting the HIV critics

For the admissions of Moore’s paper in the course of its review and conclusion are of exactly that kind. They unmistakably deny the possibility that HIV will have any significant effect on the body after antibodies clear it from the bloodstream, for the simple reason that there just isn’t enough left in the blood to have any biological effect. That is the answer to the question in his title that Moore himself gives. In doing so, he removes the essential prop of the entire HIV∫AIDS system.

Moore himself thus stands revealed as the HIV∫AIDS dissidents best friend, a man who from the heart of the establishment has had the courage to state that the emperor paradigm has no clothes. Moore, in fact, turns out to be a second Duesberg.

This is a very brave man, a man whose urge to investigate, find and announce the truth cannot be gainsayed by considerations of affiliation or funding, or even having, in the form of a notorious Op Ed piece, taken a firm stand for falsity in the pages of the New York Times.

Moore, the new Duesberg?

However, we realize that few readers are going to take this from us on faith, after all Moore has put the dissidents through, including even trying to attack their jobs through phoning up their employers. So we are happy to give chapter and verse, from this paper and a couple of others.

What we will reveal will suggest to the historians among us that when Duesberg gets his combined double Nobel for the solution to AIDS and for peace, it is not impossible that standing beside him proudly will be the once perfidious Moore, newly revealed here as the savior of AIDS patients from mismedication and deliverer of the world from the lethal infection of the AIDS meme.

Uprooting the foundation

So let’s see what the paper says. First of all, in this pathbreaking Virology review, Moore debunks the papers over the past decade in which gp 120, the surface envelope glycoprotein of HIV-1, has been added to cells in vitro, ie to human T cells in a lab dish, on the false assumption that this mimics the effect of gp120 in the live bloodstream. He writes that

“the outcome is generally that gp120 can kill a target cell or perturb its normal functions, and it is assumed that what is observed in vitro [in the lab] is relevant in vivo [in the body].”

The purpose of Moore’s review, in fact, is to see whether this is correct or not. Is there enough gp120 in the blood in vivo to do anything? Or are HIV researchers overlooking the effects of antibodies, which may block the effects seen in the lab dish and prevent them from occurring in the body?

Since this is the function of antibodies, all present may already feel they know the answer, which is Yes, HIV lab researchers evaluating the effect of gp120 have been overlooking the effects of protective antibodies in the live bloodstream.

Antibodies defeat HIV

Seventeen years after Peter Duesberg said the same thing, this indeed is the answer that Moore will arrive at. In the living patient antibodies defeat HIV and clear it from the blood stream so effectively that it can have no effect on T cells or anything else. End of story. HIV is not a lethal invader of the body biological, it is quickly seen off by the immune system of a healthy person.

“Our intent is to question whether such an extrapolation is reasonable on quantitative grounds, particularly when the presence of antibodies (Abs) in the plasma of HIV-1-infected persons is taken into account.”

Overestimates of gp120 in the blood

Moore first cites a bunch of studies to show the range of gp120 concentrations used in experiments, which have varied from 1pM to 1uM. Naturally some of these have found toxic effects, since if you add enough of anything to a culture you’ll get a toxic effect, and contamination with bacteria is common in labs, yielding endotoxins from their walls. But the problem here, he says, is that the papers everyone has relied on for the past decade or more overestimate the amount of gp120 in the blood of HIV+ people.

“Two papers are usually cited to suggest that gp120 concentrations used in vitro resemble those in bodily fluids, specifically plasma… Our impression is that these papers are often either cited incorrectly or misunderstood.”

He goes into more detail, which we will hide from those uninterested in the details.

The papers are Gilbert et al, (Enzyme-linked immunoassay for human immunodeficiency virus type 1 envelope glycoprotein 120, in the Journal of Clinical Microbiology, 29 (1), pp 142-147) 1991, and Oh et al (Identification of HIV-1 envelope glycoprotein in the serum of AIDS and ARC patients, in the Journal of AIDS 5 (3) , pp 251-256) 1992. Both are rejected by Moore as misleading, and he looks more favorably in a later paper, Gilbert et al, 2003 (Long term safety analysis of preventive HIV-1 vaccine evaluated in AIDS vaccine evaluation group NIAID-sponsored Phase 1 and Phase 2 clinical trials, Vaccine 21 (21-22), 2933-2947).

“Oh et al detected gp120 in a majority of AIDS patients’ sera in the range 0.1-0.8 nM. No gp120 was found in the sera of HIV-1 infected individuals with AIDS related complex (ARC). Thus, only in sera from people at the late clinical stages of infection, when HIV-1 antigen levels tend to rise, was free gp120 ever, apparently, detectable. However, gp120 in complex with antibody (Ab) was found in a larger proportion of sera, a point to which we shall return.”

Translation: Oh’s finding is that only when people got really sick and their immune system was having trouble coping was any free viral envelope protein detectable floating around in the bloodstream.

Otherwise, the viral envelope protein was only detected with antibodies attached, indicating as other studies have shown that the immune system does such a good job knocking out HIV with antibodies that there isn’t a detectable level in an AIDS patient’s bloodstream until they fall really ill, when the immune system is crippled and lets some HIV run loose for lack of antibodies.

Interestingly, this is going to be Moore’s final message, though he actually rejects the findings of this paper by Oh. Our interpretation of his conclusion might be phrased as follows, though we are not giving you an actual Moore quotation: In general, a healthy immune system knocks out HIV and its proteins, period, and there is no need for any vaccine, thank you very much. Yours truly, John Moore.

In his corrective review Moore then compares the Gilbert study of 2003, a different paper from a different Gilbert, where gp120 was detected only in the range 2-20 pM, and only in a minority of AIDS and ARC patients who were p24 antigenemic, ie with concentrations one to two orders of magnitude lower than the Oh study. The two studies (Oh 1991 and Gilbert 2003) do not agree with each other, therefore, and shouldn’t be cited as if they did, he says:

In contrast, Gilbert et al. (2003) detected gp120 only in the range 2–20 pM, and then only in a minority of sera from p24-antigenemic AIDS and ARC patients. The plasma gp120 concentrations detected by Oh et al. were thus one to two orders of magnitude higher than those described by Gilbert et al. (2003). Hence, the two papers should not be cited as agreeing with each other.

He then describes the methods used in each to see why the difference, and in a confused discussion finds that Oh used a method which is “questionable at best” in its ability to detect and quantify gp120 in plasma, and undoubtedly the later Gilbert study is right to lower the estimate of gp120 concentration in the bloodstream. He concludes a slew of papers have been written by the HIV∫AIDS club based on erroneous assumptions that over estimate gp120 concentrations in plasma, especially when the level of viremia is considered (even at high levels, eg a million per milliliter, the protein is hardly found – it’s 2-4 orders of magnitude lower ie 100 to 10,000 times lower than the claimed levels used in experiments).

Moore confesses – he found it first and failed to publish!

Moore moves on to discuss the level of viremia in plasma and what does he have to say? Why, that Gilbert et al.(2003) had tried mixing gp120 with human serum only to find it significantly reduced the gp120 signal and that if you add a lot of HIV positive blood, the gp120 is entirely knocked out by the antibodies in the plasma!

Not only Gilbert, moreover, has found this. Moore himself now confesses he observed the same effect many years ago in experiments which he never published!

Why didn’t Moore publish sooner?

In other words, Moore found many years ago that human antibodies thoroughly stymied the virus by attaching to the free viral envelope gp120, and thus no doubt to the virions, and somehow failed to publish this finding! Could it be that he was not anxious to spoil the global vaccine initiative led by his long time pal and sponsor David Ho, and tactfully restrained himself from putting into print what would have stymied Ho by showing there was no need for a vaccine against HIV at all, since it vaccinated against itself very well. Surely not?

Surely there must have been some less political motive for Moore’s odd lack of publication of this stupendous result, which would have raised the curtain of fear from around the Virus to demonstrate that it was rendered powerless by the natural responses of any healthy person?

The many millions that would have escaped the shame, despair, fear of death and prison, and the general self deteriorating panic that overcame them on hearing they were under a death sentence from an undetectable virus, one that eventually works its deadly magic in a way as yet unknown to science to bring them down with ghastly internal and external rot and speed them into the grave after a lull of apparently healthy life of ten or twenty years or more from the time of infection, these millions might wish he had spoken up earlier on a more prominent stage.

But they can at least be grateful to John P. Moore for at last if rather belatedly publicizing to the few readers of this obscure Virology paper his watershed finding, which fits so well the analysis of Peter Duesberg seventeen years earlier which pointed out exactly the same thing, since it was by then already demonstrated in the literature that no one was bothering to read any more.

But since Duesberg’s papers have proved to be apparently too difficult to read and respond to by his peers such as Robert Gallo, Anthony Fauci, and David Baltimore, who are far too busy saving lives, it apparently took a minor officer of the paradigm propaganda and promotion army in the service of HIV to come right out and say it, and confirm Duesberg’s point, after 17 years.

Here’s the beef

Anyone who doubts what we have to say must read it for themselves, of course. So here is the following paragraph of John P. “Truthteller” Moore’s breakthrough review, which can now be compared to those of Peter Duesberg if not in literary quality or analytical cogency at least in its power to affect events, for this is what the world has been waiting for, confirmation from the HIV paradigm A team that HIV (all its interactions depend on this protein, gp120) is defeated by human antibodies, and there is no need for the billion dollar global vaccine effort which has so far resulted in more than twenty ineffectual stabs at producing a vaccine to engender antibodies to defeat HIV, antibodies which HIV itself does very well at exciting all by itself, to a level that already utterly defeats its supposed depredations because the HIV is entirely neutralized and reduced to a harmless level in the blood which is undetectable without PCR, which is the only way the negligible and biologically irrelevant quantities of the viral sequence in human blood can be magnified geometrically into something significant and detectable.

Here it is, the paragraph which makes history, and in our opinion places John Moore one step closer to a Nobel side by side with Peter Duesberg for having the public spirit, the guts and the undeniable truthtelling urge to inform the world of the reality of the harmlessness of HIV, whatever the dispproval, scorn, calumny and rejection which may now be heaped upon his irremediably scientific head by David Ho, Bob Gallo, Anthony Fauci, and David Baltimore, the nobles of the court of HIV∫AIDS, where the Emperor HIV is now revealed to have no clothes of pathogenicity at all.

A related issue, approached by Oh et al and addressed more directly by Gilbert et al (2003) is that of interference by plasma antibodies. Gilbert et al (2003) found that mixing gp120 with control human serum significantly decreased the subsequent signal and that high titers of HIV-1+ sera could abrogate the signal completely. One of us (J.P.M.) observed much the same effect in unpublished experiments many years ago, using a capture enzyme immunoassay based on Ab D7324 and a polyclonal anti-gp120 serum. Thus, when a known amount of gp120 was spiked into different HIV-1+ sera, the anti-gp120 Abs present interfered significantly with gp120 detection, and to an extent that varied greatly between the sera. Indeed, it was impossible to judge from the assay readout what amount of gp120 had been added to the different HIV-1+ sera. Therefore, any estimation of how much gp120 was naturally present in the HIV-1+ sera was clearly problematic. The same concerns apply to p24 antigen quantification in the presence of plasma anti-p24 antibodies: only when immune complexes are dissociated, for example by the use of heat, can p24 concentrations be properly determined (Schupbach and Boni, 1993).(Emphasis added.)

Translation: Mixing human HIV+ blood with viral envelope gp120 results in its complete effective eradication by the HIV antibodies in the serum, So if you expect to measure the level of gp120 in the blood of a healthy human, don’t bother. Same applies to p24, another component of HIV and an antigen that antibodies also neutralize out of sight. All you will get to measure is antibodies (Abs).

Which is precisely what “AIDS tests”, tests for HIV, actually measure – antibodies! Surprise!

Moore’s inner tension

An even bigger surprise is that the estimable Moore cannot resist fessing up he found this out years ago by experimenting and failed to alert the public and other scientists to his discovery by publishing his result.

Clearly the pressures against this exemplary truthteller must have been immense to prevent this innately high integrity scientist from doing his duty in this regard, and so we redouble our praise for his giving in to the impulse at long last. What measure of pyschological inner conflict was playing out in Moore’s combative psyche during this process we cannot gauge, but we do know that the decision to go public cannot have been undertaken lightly.

A Samson of whistleblowers

For here Moore is undermining the chief pillar of the paradigm he has so vociferously supported in the last couple of years. He is in effect a whistleblower in the game in which he has been a chief player. Among whistleblowers he is now joining the exalted ranks of whistleblowers who have changed history.

He is in fact a Samson of whistleblowers, whose muscular arms have been wrapped around the biggest and thickest pillar of the temple of HIV∫AIDS, and with a final heave has uprooted it from the marble floor and tossed its broken halves away from him as the entire edifice has come apart above him, threatening to kill him at the same time as the horrified high priests whose armed guard he has recently commanded.

Why Moore went ballistic

Of course it appears that having let this tiger sized cat out of the bag in the narrow confines of a journal read only by the HIV club Moore seems to have chickened out, abandoned his new policy of public acknowledgement of real science and conducted ever more fierce attacks on HIV critics in his Times Op Ed piece, his AIDSTruth.org site and in email warfare with Harvey Bialy. Could it be that Fauci et al made it perfectly clear that he had gone too far? Surely not. After all, the AIDS generals have never been very keen on discussing the reality behind HIV and AIDS science in public themselves, so why should they encourage Moore to be so loud in his denials?

We conclude that it must have been the torment of having his brief moment in the fresh air of honest science curtailed that twisted Moore into some kind of psychological pretzel of inner conflict, and led to his recent ungentlemanly conduct in making excessive remarks even including the humble host of this untrumpeted blog, using such undignified words as “slime” and so forth.

Only the torment of inner conflict can account for this unexpected phase of Moore’s fine career, in which he has temporarily left behind the civility inculcated into his combative character by Downing, his respectable Cambridge college.

We want to encourage him to choose the Dr Jekyll side of his recently Mr Hyde character by supporting him completely in pursuing his 2004 path of honest admission in every way we can. We would encourage him by noting that Robert Gallo confirmed what he has said in his testimony to the Adelaide court which helped block the appeal of Parenzee against his jail sentence (see earlier posts). Gallo admitted that HIV was ineffectual against antibodies in a normal healthy person. But then so did Robin Weiss, the British equivalent of Robert Gallo, back in 1985 (R. A. Weiss et al, Neutralization of HTLV-III by sera of AIDS and AIDS-risk patients, Nature 316:69-72, 1985). Of course, the party line since then has been that HIV mutates too fast for antibodies to keep up. Not true, according to at least one mainstream paper which finds that the body’s antibodies keep up very well with HIV’s mutant escapism (D. D. Richman et al. Rapid evolution of the neutralizing antibody response to HIV type 1 infection. Proc. Nat. Ac. Sci.100:4144-4149, 2003.

Nails in the HIV coffin lid

Moore makes other confirming points in the article, just in case anyone thinks we are quoting selectively and giving a false impression. Here are the main ones:

The methods that have been used to date are not any use in estimating how much gp120 there is in the blood of HIV+ people:

Taken together, the uncertainty about the efficiency of gp120 capture, the extent of cross-reactivity of the detecting Abs with any gp120 present in plasma (at least in the assay used in Oh et al), and the interference by plasma anti-gp120 Abs, all but preclude any accurate estimate of plasma gp120 concentrations by the methods that have been used to date….The limitations of the published assays need to be taken into account when these papers are cited (Gilbert et al 2003 and Oh et al).

His guess is that these papers probably overestimated gp120 levels in plasma in vivo by two to four orders of magnitude (100x-10,000x).

It can be calculated that a plasma viral load of 10^6 virions/ml – a high level for chronic HIV-1 infection – corresponds to only 0.03-0.07 pM of virion associated gp120 and 2-3 pM p24. While this concntration of virion-associated p24 is somewhat below the upper range of p24 of total p24 in plasma (Ledergerber et al 2000) this gp120 concentration is between two (Gilbert et al, 1991) and four (Oh et al, 1992) orders of magnitude lower than the often cited values.

For, as he has already noted, the plasma antibodies neutralize most of the gp120:

We noted above that plasma anti-gp120 Abs mask the detection and quantification of gp120. The same antibodies have a very significant effect on the receptor interactions of any gp120 that is present in plasma. Abs to gp120 are usually present at high enough concentrations in plasma to bind up most of the gp120 present.

The antibodies in plasma are sufficient to prevent pretty much all binding of gp120 to CD4 or the co-receptors:


Thus, in the presence of undiluted HIV-1+ plasma, as occurs in vivo, there would be effectively no binding of gp120 monomers to CD4 or the co-receptors. This is rarely accounted for in the design and interpretation of in vitro studies with recombinant gp120, but it always should be.

Moore goes on to say that perhaps antibodies would be less effective on gp120 hiding in the central nervous system or other tissue locales, where they are present only at low levels. There is no way of telling what the outcome might be, he says. But it seems plausible that gp120 could be present in places other than the blood at much higher concentrations than in the plasma, for example, the interstitial spaces in lymph nodes. Such possibilities are hard to imitate in experiments, so he is forced to “conclude that the relevant gp120 concentrations are essentially unknown.”

The bottom line

The bottom line is that the levels of gp120 present in plasma in vivo “are far below” the levels where they have significant effects on cells in vitro ie in the lab. And any experiments must take into account the effects of antibodies which are present in vivo.

As noted above, HIV-1 positive serum antibodies will have much the same effect as the specific MAbs (monoclonal antibodies), and their presence in vivo must be taken into account.

Oops! Moore tries to cloak his realism

Having reached this rather startling set of conclusions, amounting to an admission that the paradigm “HIV causes AIDS” is a non starter given the power of human antibodies.to wipe out the virus in the blood, and its proteins, Moore then does a pretty dance to salvage his respectability with his HIV∫AIDS cohorts before he is cast into as deep a dungeon as Peter Duesberg for giving wrong answers to the scientific Inquisition.

We do not argue that gp120 could never have a biological effect on cells in vivo via receptor-mediated interactions. Nor is it impossible that virions could influence cellular processes in vivo independently of receptor-mediated fusion events.

We do, however, argue that it is not an adequate mimic of in vivo biology simply to add free gp120 (or virions) to target cells in vitro in amounts that are apparently several orders of magnitude greater than in body fluids…(The two decade-old) papers are not consistent with each other, and the more frequently cited study, by Oh et al, has serious design flaws that may cast doubt on the gp120 concentrations it promulgates. The much lower gp120 concentrations recorded by Gilbert et al (2003) are likely to be closer to true levels. And the presence of plasma anti-gp120 Abs that block receptor binding should inform the design of in vitro experiments…. Some of these considerations apply, of course, to other studies of similar design that use high concentrations of other HIV-1 proteins, such as Tat and Vpr, in vitro, in the hope that this is relevant to pathogenesis.

Sadly, as you can see, it seems that Moore could not bring himself to deny his result for very long, and immediately stated it again, just to clinch it in the minds of all listeners.

What’s more, he broadened it to make sure that readers understood that what he was saying applied not only to the envelope protein gp120 of HIV but other major proteins and the virions themselves (virions are free floating virus outside the cell; provirus is its embodiment inside the cell DNA). Antibodies deal with all these variations, it is clear, if they are found in the bloodstream.

Gentlemen, your experiments are worthless

In other words, Come on guys, stop doing experiments trying to gauge the supposed destructive effect of HIV virions or its proteins on CD4 cells in the blood by throwing gp120 or any of the others into a dish of target cells when in the body there are antibodies which defeat HIV and its proteins before it can do anything to speak of.

Doing such experiments is rather like planning the Normandy invasion of the Second World War but leaving out the Germans. In the case of HIV this is likely to be even more misleading because in every healthy human there are enough German antibodies to repel boarders and throw the English and the Americans HIV virions and proteins back into the sea. An invasion by HIV is a D Day which rapidly turns into a Dunkirk.

Bravo! John P. “Truthteller” Moore for pointing to this long ignored truth.

Here is the paper, for reference: Is there enough gp120 in the body fluids of HIV-1-infected individuals to have biologically significant effects?

doi:10.1016/j.virol.2004.03.003

Minireview

Is there enough gp120 in the body fluids of HIV-1-infected individuals to have biologically significant effects?

P. J. Klasse and John P. Moore,
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, USA
Received 16 January 2004; Revised 17 February 2004; accepted 2 March 2004. Available online 26 April 2004.

“Is there enough gp120 in the body fluids of HIV-1-infected individuals to have biologically significant effects?” [Virology 323 (2004) 1–8]
Virology, Volume 327, Issue 1, 15 September 2004, Pages 155-155
P.J. Klasse and John P. Moore

Over the past decade, many publications have described experiments in which the recombinant monomeric form of the gp120 surface envelope (Env) glycoprotein of human immunodeficiency virus type 1 (HIV-1) has been added to cells in vitro (Fig. 1). The ensuing cellular responses (e.g., activation of signal transduction pathways resulting in cytokine release, chemotaxis, proliferation, anergy, or apoptosis) are monitored. The outcome is generally that gp120 can kill a target cell or perturb its normal functions, and it is assumed that what is observed in vitro is relevant in vivo. Our intent is to question whether such an extrapolation is reasonable on quantitative grounds, particularly when the presence of antibodies (Abs) in the plasma of HIV-1-infected persons is taken into account. We cite only a small selection from this abundant literature, to illustrate the range of active gp120 concentrations reported.

Fig. 1. (a) The HIV-1 envelope glycoprotein (Env) complex consists of trimers of non-covalently linked heterodimers of an outer, receptor-binding moiety, gp120, anchored to a transmembrane protein gp41, which is involved in the fusion of the viral envelope with the cell membrane. The gp120 moiety is shown (left) interacting with the four-domain receptor, CD4. This binding induces a conformational change that facilitates the interaction of gp120 with a coreceptor, CCR5 for R5 virus and CXCR4 for X4 virus (right). The interactions of gp120 with CCR5 and CXCR4 are weak in the absence of CD4. (b) A monomer of gp120 is shown to undergo interactions corresponding to those in (a). This scheme is reproduced in many experiments making use of monomeric recombinant gp120. A significant degree of binding and many experimental effects are only obtained at much higher concentrations than what could realistically be present in extracellular fluids in vivo (top). A complex between gp120 and soluble CD4 is shown to interact with a coreceptor on the cell surface. In the absence of CD4, the affinity of gp120 for CCR5 or CXCR4 is low (bottom, left). Specific antibodies prevent gp120 from binding to CD4; this also precludes further, downstream contact with the coreceptor (bottom, right). The blocking effect of antibodies is likely to occur in vivo except in certain tissues where their concentration is lower, such as the central nervous system. (c) An HIV-1 virion is shown schematically. The Env trimers of heterodimers (gp120 and gp41) stud the phospholipid bilayer that surrounds the viral Gag proteins and RNA genome. The copy-number ratio of the Gag to Env in virions is 50.

In the in vitro experiments, the gp120 concentrations vary from 1 pM to 1 μM (ca. 0.12 ng/ml to 120 μg/ml, as 1 nM ≈ 0.12 μg/ml, e.g. Arthos et al., 2002; Chirmule et al., 1990; Davis et al., 1997; Esser et al., 2001; Goldman et al., 1994; Herbein et al., 1998; Hesselgesser et al., 1998; Huang et al., 2001; Kanmogne et al., 2001; Keswani et al., 2003; Kornfeld et al., 1988; Mann et al., 1987; Masci et al., 2003; Munshi et al., 2003; Oyaizu et al., 1990; Schneider-Schaulies et al., 1992; Tamma et al., 1997; Vlahakis et al., 2003; Wahl et al., 1989; Weinhold et al., 1989; Weissman et al., 1997 and Yao et al., 2001). Sometimes biological effects occur only at the higher end of the range, although particularly in neuronal cell systems lower gp120 concentrations can be active. In those systems, the primary effects may be partly on microglial cells, which are reported to amplify secondary effects on neurons (cf. Garden, 2002; Kaul and Lipton, 1999 and Keswani et al., 2003, reviewed in Kaul et al., 2001).

Historical measurements of plasma gp120 concentrations

Two papers are usually cited to suggest that the gp120 concentrations used in vitro resemble those in body fluids, specifically plasma (Gilbert et al., 1991 and Oh et al., 1992). Our impression is that these papers are often either cited incorrectly or misunderstood. What do they, in fact, report? Oh et al. detected gp120 in a majority of AIDS patients’ sera in the range 0.1–0.8 nM. No gp120 was found in the sera of HIV-1-infected individuals with AIDS-related complex (ARC). Thus, only in sera from people at the late clinical stages of infection, when HIV-1 antigen levels tend to rise, was free gp120 ever, apparently, detectable. However, gp120 in complex with antibody (Ab) was found in a larger proportion of sera, a point to which we shall return. In contrast, Gilbert et al. (2003) detected gp120 only in the range 2–20 pM, and then only in a minority of sera from p24-antigenemic AIDS and ARC patients. The plasma gp120 concentrations detected by Oh et al. were thus one to two orders of magnitude higher than those described by Gilbert et al. (2003). Hence, the two papers should not be cited as agreeing with each other.

Both papers rely on capture enzyme-immunoassays to quantify gp120. The assay of Gilbert et al. (2003) uses a soluble form of CD4, the primary receptor for gp120 (see Fig. 1), to capture gp120 onto a solid phase. The bound gp120 is then detected with a polyclonal sheep Ab raised against a peptide from the C terminus of gp120 of the T-cell line-adapted isolate IIIB. This antibody, D7324, cross-reacts strongly with gp120s from multiple HIV-1 strains, particularly within subtype B but also outside it (Moore and Jarrett, 1988 and Moore et al., 1994b). As soluble CD4 is pan-reactive with properly folded gp120s, the assay used by Gilbert et al. (2003) is relatively little affected by gp120 sequence diversity. In contrast, Oh et al. employed a polyclonal serum to gp120 of the IIIB isolate for capture, with a monoclonal Ab (MAb) to the V3 loop of IIIB gp120 as the detection reagent. Details of the specificity of the latter MAb are not provided, but it is stated “to have 10–15% cross-reactivity with other strains”. Regardless of whether this value refers to the extent of binding or the proportion of test gp120s that it reacted with, it is now well understood that the recognition of gp120 from primary viruses by IIIB-specific V3-loop MAbs is usually poor. The cross-reactivity capabilities of the assay used by Oh et al., and hence its ability to detect and quantify gp120 in plasma, is, therefore, questionable at best. This assay would be expected to underestimate plasma gp120 content by failing to recognize gp120 from the infecting strain. However, its results suggest that gp120 is present in plasma at surprisingly high concentrations, both relative to what was found by Gilbert et al. (2003) and to viremia, as discussed below.

A related issue, approached by Oh et al. and addressed more directly by Gilbert et al. (2003), is that of interference by plasma antibodies. Gilbert et al. (2003) found that mixing gp120 with control human serum significantly decreased the subsequent signal and that high titers of HIV-1+ sera could abrogate the signal completely. One of us (J.P.M.) observed much the same effect in unpublished experiments many years ago, using a capture enzyme immunoassay based on Ab D7324 and a polyclonal anti-gp120 serum. Thus, when a known amount of gp120 was spiked into different HIV-1+ sera, the anti-gp120 Abs present interfered significantly with gp120 detection, and to an extent that varied greatly between the sera. Indeed, it was impossible to judge from the assay readout what amount of gp120 had been added to the different HIV-1+ sera. Therefore, any estimation of how much gp120 was naturally present in the HIV-1+ sera was clearly problematic. The same concerns apply to p24 antigen quantification in the presence of plasma anti-p24 antibodies: only when immune complexes are dissociated, for example by the use of heat, can p24 concentrations be properly determined (Schupbach and Boni, 1993).

Taken together, the uncertainty about the efficiency of gp120 capture, the extent of cross-reactivity of the detecting Abs with any gp120 present in plasma (at least in the assay used by Oh et al.), and the interference by plasma anti-gp120 Abs, all but preclude any accurate estimate of plasma gp120 concentrations by the methods that have been used to date. Of note is that Gilbert et al. (2003) found no correlation between plasma p24 and gp120 concentrations, which may reflect differences in the extent of Ab complexing with the two antigens. The limitations of the published assays need to be taken into account when these papers are cited, particularly in respect of the high gp120 concentrations reported by Oh et al.

Alternative estimates of plasma gp120 concentrations

What concentrations of gp120 could be expected in HIV-1+ plasma? Plasma concentrations of the viral Gag protein (Fig. 1) p24 provide a useful guide. Most plasma p24 antigen is normally Ab-complexed or virion-associated. But after its release as a free protein, it is detected at concentrations <40 pM (Ledergerber et al., 2000), that is, just above the 2–20 pM reported for free gp120 by Gilbert et al. (2003). If virions were the only source, gp120 concentrations would be 40- to 60- fold lower than those of p24 (Chertova et al., 2002; Layne et al., 1992 and Zhu et al., 2003). It can be calculated that a plasma viral load of 106 virions/ml—a high level for chronic HIV-1 infection—corresponds to only 0.03–0.07 pM of virion-associated gp120 and 2–3 pM p24. While this concentration of virion-associated p24 is somewhat below the upper range of total p24 in plasma (Ledergerber et al., 2000), this gp120 concentration is between two (Gilbert et al., 1991) and four (Oh et al., 1992) orders of magnitude lower than the often cited values.

Gp120 that is not associated with virions could potentially be derived from infected cells. The envelope glycoprotein complex (Fig. 1) is produced and processed via the secretory pathway, whereas the Gag precursor is synthesized on free ribosomes in the cytoplasm. Although virions incorporate approximately 50-fold fewer Env than Gag molecules when they bud from cellular membranes (see Fig. 1c) (Chertova et al., 2002), we do not know the ratio of Gag to Env in infected cells in vivo. It could be argued that the majority of Env never exits from the secretory pathway, and that significant additional amounts of gp120 is released from dead or moribund cells as “viral debris” (Parren et al., 1997). However, some of this debris would not interact with receptors and such lysed cells would also release p24. Hence, it is hard to explain how gp120 proteins capable of receptor binding could be present at higher concentrations than p24.

The effect of plasma antibodies on gp120–receptor interactions

We noted above that plasma anti-gp120 Abs mask the detection and quantification of gp120. The same antibodies have a very significant effect on the receptor interactions of any gp120 that is present in plasma. Abs to gp120 are usually present at high enough concentrations in plasma to bind up most of the gp120 present. The ratio [Ab]/Kd determines their degree of binding to gp120, in accordance with the law of mass action (Klasse and Sattentau, 2002). Anti-gp120 Ab concentrations have been estimated to be in the micromolar range (Binley et al., 1997); so for high-affinity binding (Kd < 10 nM), the occupancy of gp120 by Abs should approach saturation. And the titers of Abs able to inhibit the binding of gp120 to CD4 (and hence indirectly to CCR5 or CXCR4) are in the range 1:100 to 1:1000 in HIV-1+ sera (Callahan and Norcross, 1989 and Moore et al., 1994a). Thus, in the presence of undiluted HIV-1+ plasma, as occurs in vivo, there would be effectively no binding of gp120 monomers to CD4 or the co-receptors. This is rarely accounted for in the design and interpretation of in vitro studies with recombinant gp120, but it always should be. Less complexing of gp120 by Abs would occur in some tissue locales. For example, Abs are present only at low levels in the central nervous system, even when HIV-1 infection causes intrathecal Ab production and blood–brain barrier leakage (Goudsmit et al., 1987 and Kaul et al., 2001). In general, Ab concentrations in different tissues are likely to vary considerably from those of gp120 and virus. Predicting the net effects of variations in relative and absolute concentrations of Ab, gp120 and virus is a complex task that we do not attempt here. Concentration of gp120 in tissues The putative levels of gp120 measured, or plausibly present, in plasma are far below some of those that have significant effects on cells in vitro. But could the latter concentrations nevertheless be biologically relevant by matching those in compartments other than blood? The gp120 concentrations in, for example, the interstitial spaces of lymph nodes or other solid organs are unknown. Nevertheless, if the greater density of cells, the smaller extracellular space and the possibly slower dilution kinetics were quantitatively factored in, it seems plausible that gp120 could be present within interstitial lymph node spaces at concentrations several orders of magnitude higher than in plasma. Furthermore, if small secluded spaces are created during cell-to-cell transmission of HIV-1 and HTLV-1, the so-called virological synapses (Igakura et al., 2003 and Jolly et al., 2004), then viral proteins may be present at high local concentrations in those clefts. In vitro studies involving Env-producing cells may, therefore, be more realistic than those using soluble, recombinant gp120 (Castedo et al., 2001; Castedo et al., 2002 and Jekle et al., 2003). However, the gp120 concentration gradients produced by such cells are difficult to assess. And membrane-associated Env may differ from soluble gp120 in, for example, its qualitative effects on T-cell activation (Schwartz et al., 1994). Another relevant complication is that gp120 from X4 viruses, but not R5 viruses, binds to heparan-sulphate glycosoaminoglycan (GAG) moieties of proteoglycans, and thereby can be retained within tissues both in the extracellular matrix and on cell surfaces (Moulard et al., 2000 and Ugolini et al., 1999). GAGs are present on the surface of many cell types (Ugolini et al., 1999). An analogy may be drawn between gp120 and chemokines that, in vivo, do not seem to act as free proteins. Chemokines, instead, interact with G-protein-coupled receptors while in the form of surface-bound GAG complexes that establish haptotactic gradients in tissues (Proudfoot et al., 2003). Such potentially modulating effects of the tissue environment complicate the rational design and interpretation of in vitro experiments, which by necessity simulate in vivo conditions imperfectly. We conclude that the relevant gp120 concentrations in the organism are essentially unknown. Affinity of gp120 for its receptors and the influence of receptor occupancy Ultimately, any consequences of local concentrations of gp120 depend on its affinity for the relevant receptors and the degree of binding required for signals to be transduced. Several effects of gp120 are mediated through CD4 binding, either directly or indirectly through subsequent CD4-dependent interactions with a chemokine coreceptor. The Kd of gp120 binding to CD4 is in the range 1–10 nM (Ashkenazi et al., 1990; Ivey-Hoyle et al., 1991; Moebius et al., 1992 and Moore, 1990). That is higher even than the concentrations reported by Oh et al. and 1000-fold higher than those found by Gilbert et al. (2003). However, gp120 may also bind with high affinity to DC-SIGN and other C-type lectin receptors (Geijtenbeek et al., 2002 and Turville et al., 2002), as well as to the GAG moieties of proteoglycans (Moulard et al., 2000 and Ugolini et al., 1999). Although the latter interactions of soluble monomeric X4 gp120 are readily reversible (Mondor et al., 1998b), binding to such accessory attachment molecules could raise the effective gp120 concentrations available for other receptor interactions. Quite distinct degrees of binding, or occupancies, of cellular receptors may be required to exert the different effects on the target cells that we are discussing. But generally, the occupancy can be estimated from the formula [[gp120]/Kd]/[[1 + [gp120]]/Kd] (Klasse and Moore, 1996). Thus, for 99% occupancy, the concentration of gp120 must be >100-fold above Kd. That means 0.1–1 μM for CD4 binding. Indirect effects of gp120 on T-cell activation, mediated by blocking the interactions of antigen-MHC class II with CD4 and the T-cell receptor (Chirmule et al., 1995), would quite plausibly require the binding of gp120 to a large proportion of CD4 molecules. Some effects involving signaling via cell-surface receptors are, in principle, different. Thus, much lower occupancies, produced by gp120 concentrations close to or below Kd (Munshi et al., 2003) could conceivably be effective. Most biological effects would nevertheless require a detectable occupancy. Hence, we face a double conundrum: either active concentrations of gp120 are above Kd for receptor binding, which may not be realistic under in vivo conditions; or they are lower, which makes it difficult to explain how substantial binding could be achieved.

Some effects of gp120 are suggested to occur independently of CD4 (for example, Iyengar et al., 1999). The affinity of gp120 for CCR5 and CXCR4 in the absence of CD4 is usually found to fall below the limit of detection. Thus, there was no detectable X4 gp120 binding to CXCR4 at concentrations as high as 0.25–0.5 μM (Doranz et al., 1999 and Mondor et al., 1998a), and little binding of R5 gp120 to CCR5 at 0.4–0.5 μM (Trkola et al., 1996 and Wu et al., 1996). There is, however, one starkly contrasting report of higher-affinity gp120 binding (Kd ≈ 70 nM) to CXCR4 on CD4-negative, differentiated neuronal cells (Hesselgesser et al., 1997). The binding of soluble-CD4–gp120 complexes to CCR5 has a Kd of 4 nM (Doranz et al., 1999 and Wu et al., 1996), and to CXCR4 of 200 nM (Babcock et al., 2001). Despite the poor or controversial capacity of gp120 to interact directly with CCR5 or CXCR4, a pathophysiological role for the interaction of gp120 with these molecules on neurons and astrocytes has been proposed (Kaul et al., 2001). If the highest reported gp120–CXCR4 affinity is accurate (Hesselgesser et al., 1997), then the dose dependence of X4 gp120-mediated apoptotic effects via CXCR4 on CD4− neuronal cells is as expected, that is, a significant and increasing response from 20 nM to 1 μM (Hesselgesser et al., 1998). But whether that extremely high concentration range is relevant in vivo remains to be confirmed. In contrast, much lower concentrations of gp120 (0.1–200 pM) have also been found to be neurotoxic, with and without intermediary effects on Schwann and glial cells (Keswani et al., 2003 and Meucci et al., 1998). The occupancy of CXCR4 at gp120 concentrations in the sub-nanomolar range would be immeasurably low (<0.1%), even if we assume that the Kd ≈ 70 nM (Hesselgesser et al., 1997).

It is possible to investigate whether gp120 is bound to cells from HIV-1-infected individuals, and at what occupancy, ex vivo. The presence of gp120 attached to CD4 on the T-cell surface ex vivo has been inferred, although not directly detected (Amadori et al., 1992). But there is also a converse finding of the failure to detect specific masking of the gp120-binding site on CD4 on T cells from HIV-1-infected individuals (Kunkl et al., 1994). Resolving whether gp120 is detectable on the surface of CD4+ (or CD4−) cells ex vivo would help clarify gp120’s pathogenic role.

The outstanding task, then, is to assess and explain the occupancy of receptors by gp120 in vivo and what effects that has on the cells.

Use of virions in vitro

Some in vitro experiments have used virus-like particles or inactivated virions to study HIV-1-induced apoptosis, for comparison with the effects of recombinant soluble gp120 (Esser et al., 2001; Vlahakis et al., 2003 and Yao et al., 2001). When virus for this use is concentrated by several orders of magnitude, considerations apply that are similar to those for monomeric gp120: how well does the virion concentration used in vitro reflect what is present in vivo? Can virion densities rise to particularly high levels in certain locales, such as interstitial spaces in lymph nodes, and there exert the effects observed in vitro? The affinity of virions for target cells is unknown but liable to be the net outcome of two opposing influences. The receptor-interactive surfaces on the gp120 subunits are relatively inaccessible in the context of the virion-associated Env trimer, which will reduce the functional affinity of the interaction. Countering this, is the polyvalency effect of multiple trimers interacting with multiple receptors (as partly illustrated for murine leukemia virus; Yu et al., 1995). The binding of X4 virions to heparan sulphate proteoglycans on the cell surface is indeed more avid than that of monomeric gp120 (Mondor et al., 1998b).

Inactivated virus with a content of 0.4 nM of p24 (Esser et al., 2001), or even as high as 4 nM (Vlahakis et al., 2003), has been used in vitro. This corresponds to 8–80 pM virion-associated gp120. The degree of receptor binding that may ensue at these levels of virion-associated Env cannot be rationally predicted at present. But the maximal virus-induced apoptotic effect could not be mimicked by the corresponding amounts of monomeric gp120 or heat-denatured virions, and it required the presence of MHC class II on the virion (Esser et al., 2001). However, in another experimental system, HIV-1-induced cytolysis occurred regardless of the presence of MHC class II (LaBonte et al., 2003). Cytolysis is an alternative mechanism of cell death to apoptosis induced by receptors, and cytolysis are alternative mechanisms of cell death, cytolysis requires fusogenic Env protein, and affects only the infected cell (LaBonte et al., 2003).

The relative relevance of the experimental use of soluble Env, inactivated virions and fusogenic replicating virus to the pathogenesis of AIDS needs to be elucidated.

Improving the design of experiments using gp120

How could the design of in vitro studies using monomeric gp120 be improved (see Box 1)? The possible presence of biologically active contaminants, including endotoxins in gp120 preparations from commercial and other sources should always be considered. The use of anti-gp120 MAbs specifically to prevent gp120-CD4 or -coreceptor binding is a prudent control. As noted above, HIV-1+ serum antibodies will have much the same effect as the specific MAbs, and their presence in vivo must be taken into account. Gp120 point mutants defective for CD4 or coreceptor binding provide further controls. Thereby one can at least determine whether the consequences of sprinkling gp120 on mammalian cells depend on receptor binding, or whether they are merely attributable to contaminants in the protein preparation.

Conclusions

We do not argue that gp120 could never have a biological effect on cells in vivo via receptor-mediated interactions. Nor is it impossible that virions could influence cellular processes in vivo independently of receptor-mediated fusion events.

We do, however, argue that it is not an adequate mimic of in vivo biology simply to add free gp120 (or virions) to target cells in vitro in amounts that are apparently several orders of magnitude greater than in body fluids. Moreover, it is not appropriate to justify the amounts of gp120 used by reference to the two decade-old papers that purport to measure free gp120 in the plasma of HIV-1-infected people. These papers are not consistent with each other, and the more frequently cited study, by Oh et al., has serious design flaws that may cast doubt on the gp120 concentrations it promulgates. The much lower gp120 concentrations recorded by Gilbert et al. (2003) are likely to be closer to true levels. And the presence of plasma anti-gp120 Abs that block receptor binding should inform the design of in vitro experiments (see Box 1). Controls for gp120 purity and for the specificity of the interactions with CD4, chemokine receptors and GAGs should also be included in experimental protocols. Some of these considerations apply, of course, to other studies of similar design that use high concentrations of other HIV-1 proteins, such as Tat and Vpr, in vitro, in the hope that this is relevant to pathogenesis.

Box 1. Criteria for establishing the biological relevance of experiments using gp120 in vitro

1. Experimental concentration ranges shown to be relevant to the particular tissue compartment modeled.
2. Specificity of the receptor interactions demonstrated by use of gp120 deletion mutants or Abs blocking receptor binding.
3. Demonstration that the requisite receptor occupancy can be obtained under experimental conditions.
4. Inclusion of anti-gp120 Abs with a binding capacity (concentration and affinity) corresponding to that in the relevant tissue compartment.
5. Comparison of effects of recombinant gp120 with those of realistic levels of virions.

Acknowledgements

We are grateful to Maciej Paluch for preparation of the illustrations and to André Marozsan for discussions. This work was supported by NIH grants AI36082, AI39420 and AI41420. J.P.M. is a Stavros S. Niarchos Scholar. The Department of Microbiology and Immunology at the Weill Medical College gratefully acknowledges the support of the William Randolph Hearst Foundation.

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Corresponding author. Joan and Sanford I. Weill Medical College of Cornell University, Department of Microbiology and Immunology, 1300 York Avenue, W-805, New York, NY 10021. Fax: +1-212-746-8340.

Virology
Volume 323, Issue 1, 20 May 2004, Pages 1-8
Copyright © 2007 Elsevier B.V. All rights reserved.

24 Responses to “John P. Moore Brings Down The AIDS Paradigm (Part 2)”

  1. MacDonald Says:

    Truthseeker, it appears you, in your perfectly understandable enthusiasm for Moore, have forgotten that you have already awarded the Nobel Prize to Anthony Fauci for his seminal work on the non-correlation between viral load and CD4 cell loss, if I remember correctly.

    But perhaps you are right that JP deserves the nomination to an even higher degree. Not only is he a great humanitarian who fights unceasingly for the rights of women, children, gays and South Africans to receive lifesaving drugs, often in spite of their own stubbornness and ignorance, there is also his illustrious campaigns for freedom of the press to report verbatim the moral truths as conveyed by HIV scientists.

    What makes Moore’s impact greater even than his towering stature as a scientist and champion of every boss’s human right to fire an employee who has failed to grasp those self-evident beyond questioning moral truths is his legendary ability to turn a phrase so characteristic of the true English gentleman. In his truthtelling article above Prof. Moore, than whom none is more expert in this field, has once again succeeded in capturing the desperately fumbling nature of HIV research in one Nobel Prize worthy sentence, more specifically in one priceless word:

    “Some of these considerations apply, of course, to other studies of similar design that use high concentrations of other HIV-1 proteins, such as tat and Vpr, in vitro, in the hope that this is relevant to pathogenesis.

  2. Truthseeker Says:

    MacDonald, your hawkeyed point is taken as always, since “hope” is certainly the operative word and a fine signal of the attitude of the distinguished researchers we are dealing with.

    But you are also right on target in pointing out that we have too many candidates for the Nobel for solving AIDS, which has yet to be awarded, perhaps because the Stockholm sages and their advisors across the world (usually Nobel winners of previous years) may be less naive than the rest of the world. Or perhaps we even have a rethinker among them!

    Yes, our quandary is that there are only three names maximum allowed per Nobel, as we believe, and apart from the very genuinely distinguished scientist Peter Duesberg we now have Robert Gallo, for being the very first to show in 1984 that HIV could not possibly be the cause of AIDS, since it was found in so few patients (one third), Anthony Fauci, for discovering that the HIV is the best vaccination against itself for it not only engenders antibodies but also stimulates the production of T-cells, and now John P. Moore, for shooting himself voluntarily in both feet with his critique of experimenters who forgot about those antibodies, and confirming that we already have a vaccine against HIV in HIV.

    Perhaps this attempted displacement of Fauci by Moore in the high stakes race to share the Nobel for AIDS with Duesberg is causing a certain amount of irritation at the top of NIAID.

  3. Robert Houston Says:

    Thank you, Truthseeker, for your extraordinary and provocative new post that reveals the phenomenal hypocrisy of HIV$AIDS researcher Dr. John Moore – dissident-basher in public and closet HIV skeptic himself in technical communications that the public won’t read. His evident recognition of contradictions in the HIV hypothesis may well be the source of his vengeful fury to extirpate AIDS “denialism” as a projection of the annoying doubts in his own mind. Fortunately, some of his rancor has been directed to HIV research itself, which he has attacked as misleading, both in the 2004 review on gp120 that you discussed and in a blistering critique of HIV vaccine research the same year.

    Some readers may not realize the significance of the HIV envelope protein gp120 to HIV theory. This is the protein that forms the spikes on the surface of the virus which allows it to bind to the CD4 T-cells, to infect them, and to fuse cells together – a major basis for alleged cytopathic effects. The pivotal role of the protein was spotlighted last month by NIAID director Anthony Fauci:

    “The binding of the HIV gp120 envelope protein to CD4 on resting or activated T cells results in conformation change in the envelope, interaction with the coreceptor, and fusion of the viral and cell membranes, and it gives the HIV genome access to the interior of the cell.” –M. Johnston and A. Fauci (An HIV vaccine – evolving concepts. New Eng J Med 356:2073-81, May 17, 2007).

    Dr. Fauci and his colleague also pointed out that gp120 can act protectively as a partial vaccine: “Gp120 that had been produced in mammalian cell lines induced the highest level of neutralizing antibodies in laboratory assays that used HIV…” He also notes that “gp120 protected chimpanzees from HIV infection.” Fauci thus tends to confirm both Moore’s review and Truthseeker’s interpretation.

    HIV itself provides several proteins that elicit antibody responses and thus, as Truthseeker indicates, may be the best vaccine of all. Indeed, Cambridge University virologist Prof. Abraham Karpas has written: “The immune response to HIV can be compared to that of a live viral vaccine. It explains why most HIV-infected individuals remain well for many years.” (A. Karpas, Biological Reviews 79:911-933, 2004).

    In his 2004 review, Dr. Moore exposed the chicanery of HIV research in its claim of untoward effects by the use of levels of the gp120 protein that are 100 to 10,000 times that at which it actually occurs in an HIV-positive individual. As Truthseeker wisely notes, everything can be toxic at some level. (Try eating a meal containing 100 times the normal serving of any harmless food, e.g., instead of 4 ounces of spinach on the plate, there’d be 25 pounds!)

    In fact, a study this April found that the polyneuropathy that has been attributed to HIV’s gp120 cannot be mainly due to gp120 – even at the absurd concentrations used by HIV researchers to produce toxic effects on nerve cells – since such nerve toxicity is much more readily produced by the anti-HIV drugs themselves: ddI, ddC, d4T, and of course AZT (B. Robinson et al. J. Neurovirology 13:160-7, April 2007).

  4. Nick Naylor Says:

    Not to mention this little gem buried in the text: “gp120 point mutants defective for CD4 or co-receptor binding … “, a dastardly bit of cherry-picking no doubt. But think of how little it takes for the Mighty HIV to fail in its mission, according to this particular revelation, especially since it’s so undetectable in the first place.

  5. fraorlando Says:

    So, it is apparent that pathogenesis of aids is far from being solved. Yes, maybe after all HIV may not be the culprit. But one thing i do not understand: There is, after all, a marked correlation of HIV positivity and illness – very often Fatal illness – not only seen in drug addicts, as duesberg would point out. So, after all, what is bringing these peoples helth down. I doubt it that its only the meds – in fact i have talked to the counselor of a local aids charity. He turned ot to be very open minded, even whe i would present dissident views…its just like he saw all kinds of people, such in ‘risk groups’ and others not, being positive and coming down with OI’s and such, regardless of their lifestyles. Of course this is only anecdotal, but the question remains: what is happening to those people?

  6. Truthseeker Says:

    the question remains: what is happening to those people?

    Healthy people with no other causes of illness do not display any symptoms of HIV positivity except for scoring positive on the HIV antibody test. If people fall ill, and if they die, it is evidently from other causes, predictable and familiar, causing predictable and familiar symptoms. The causes including the following: excessive intake of recreational drugs, excessive exposure to unsanitary conditions, excessive intake of antibiotics and other measures taken to prevent or fight infections, inappropriate toxic medical treatment based on a false attribution of cause, the voodoo effect of superstitious belief in the dire diagnosis, conventional illness caused by known familiar disease interpreted as “AIDS” and not treated appropriately, and malnutrition generally and specifically of the immune system caused by lack of correct and adequate nourishment (eg lack of selenium, zinc, Vitamin B6, copper, Vitamin E, Vitamin A, Vitamin B12, etc etc etc)

    This is what the scientific literature tell us, although it is handicapped by lack of funding of studies which do not share the assumption that HIV causes illness. That bias corrupts the scientific literature, and obscures the final solution to this problem. It allows the false assumption to live on, funded by what is now hundreds of billions. Meanwhile, all anecdotal evidence is interpreted according to this assumption, as evidenced by your friendly open minded aids charity counselor.

  7. fraorlando Says:

    Well, but still people are in fact sick with progressing and often fatal immunesurpression. See, i am aware of the shoddy sciences in aids research(though its not my field of expertise, so its sometimes hard to tell…), but still i have conflicting experiences – like a doctor of mine who is also treating aids patients whose only explanation for their condition where blood transfusions with hiv positive blood – for whatever that means. And you know, this doctor is not prescribing toxic treatment, he is a naturopath and somehow manages to support their immune systems in a way so that they can recover from frequent bouts of PCP and so on…but please, i really dont know – and want to learn, so can you point me to the evidence? And what about alternative theories explaining aids -in that sense, yes i have read duesberg, but for me its somehow not adding up. His reasoning that hiv may be harmless seems conclusive, but his theories about the real causes, i dont think so, for, under normal circumstances, immune suppression would cease if you do away with chemical, iatrogenicic or nutritional etc. issues, no? But it just doesnt seem like that with aids.

    Also, i want to state my position: I am a concerned psychologist who became aware of conflicting views in regards to hiv/aids. If the viral theorie is wrong and there are better explanations for what is happening in aids, lots of suffering, mentally and physically, of people maybe wrongly diagnosed, could be relieved – so i am interested in finding out, listening to both sides….

  8. Truthseeker Says:

    This blog has to be written on the assumption that readers are prepared to read the earlier posts if they want to catch up on the conclusions reached after our extensive review, but it is always good to deal with the fundamental questions that are raised in the minds of newcomers, since that is the position we are all in on the edge – talking to newcomers unfamiliar with any of the literature, who need basic explanations which sound valid – as we try to expand understanding of the scientific view of HIV∫AIDS, as demonstrated by the literature when reviewed without the HIV assumption which has corrupted so much of it.

    When you ask that we “point you to the evidence” this is exactly what this blog does as often as possible in every post, by providing references in our ongoing activity of comparing the paradigm promotion claims with the literature of the field.

    Your question seems to divide into these parts:

    1) You accept that HIV does not seem to be a good candidate for causing the illnesses that are labeled HIV∫AIDS.

    2) You see that people are ill and dying and you ask what then is a good candidate for causing these illnesses. But we have already answered this above, by listing the factors involved, so what phenomena do you think do not fit our answers?

    3) You say that your friend is a physician whose patients can only account for their illness through the blood transfusions they have had. Does this make it true then that HIV caused their illness?

    There is no reason to think so because
    a) patients are notoriously unreliable when giving their histories
    b) blood transfusions are typically given to people whose health is threatened by other factors, eg loss of blood in an accident, where serious injury is involved, shock etc; one study found that half the blood transfusion recipients in East Coast hospitals died within the year
    c) there is no evidence that recipients of blood positive for HIV antibodies did any worse than other recipients, contrary to early claims, unless they get AZT
    d) the science shows that HIV is a entirely unlikely candidate for causing any illness under any circumstances.

    4) As you know you are talking anecdotes here which are not valued in science very highly for the reason that statistics are the only data which can be controlled for the myriad factors that make us all so individual in our biological responses, not to mention the unreliability of personal reports.

    5) If you really have read Duesberg as you say you would know all this since the claim that blood transfusion recipients especially hemophiliacs did worse when the blood was HIV positive was one of the earlier claims brought against him which he thoroughly refuted.

    6) You seem to think that somewhere there is an answer beyond the ones we have given you, but we suggest that you are overlooking the basic truth that the immune system is sensitive to failures of and imbalance in the diet especially of the trace elements which it needs to operate successfully, and if you add drugs to your system, and/or starve it of these and other nutrients, you will affect it seriously soon enough.

    Medical intervention emphasizing more and more adverse drugs and over prescription of antibiotics will disrupt microflora, allow parasites and prevent recovery, especially anti-inflammatory corticosteroids which can reduce T Cell count by over 600 in ten days, far more than claimed for any virus. Root-Bernstein reviewed a lot of factors of this kind including even acetaminophen, the oxidizing agent used as a substitute for aspirin (Tylenol, Exedrin etc.) Eat your Turkish live culture yogurt – even Danon Danactive Immunity from Gristedes will raise your T cell count, check your local TV ad!

    7) If your naturopath doctor is applying more sensible principles and his patients are still ill then you have to look for other factors. All we can say is that HIV is not a factor, according to the best scientific literature, however often John P. Moore and others like to use it as a basic assumption, a sine qua non, even when it is disproved by the very study they are writing up.

    8) It may be that you are overlooking the fact that once your immune system is weakened it may be difficult to recover it as long as the assaults from other factors continue. Also, it may be relevant that semi-tropical cities like New York are cesspools of all kinds of agents which are imported by travelers from other countries into what is becoming a notorious Grand Central Station of bacteria, viruses and parasites from once exotic regions.

  9. fraorlando Says:

    Yes, i agree with you that other explanations are possible, but as i said, for me its hard to say.
    One of such possible explanations would be a psycho-immunologic theory using Selyes’s Stress model. In a sketch: Persistent Stress due to dire Diagnosis leads to constant high levels of cortisol, which is immune suppressive, t-cell count goes down, HAART is introduced which, after some time damages the system even more because, as duesberg points out, all anti viral madications err medications are necessarily toxic to basic cell functions.
    I think this model ist testable in an animal model, like giving rats constant life threatening situations and then test how they react on HAART compared to a control…(all the way measuring immune system functions – t cells etc.)(of course before that it would be necessary to proof that HIV-positive people have also constant high levels of cortisol due to their diagnosis)…when animals show drops in t-cell count and subsequently develop aids-like diseases with or without haart, this would be a point to go from for the dissidents view, i could imagine..and also i think a model that works better is necessary to abolish the residing one, for i think its vital to publish studies that are proofing the dissident view, not only analysing the work of the orthodox scientists…

    Thanks for you input so far, i will investigate the issue further and also respond to the points you have made, need to read more on that…

  10. Nick Naylor Says:

    In line with fraorlando’s inquiry, it is obviously important to start the discussion at the very beginning … nonetheless, we’re also wrestling with and trying to synthesize thousands of reviews and research papers. There is actually a tradition for interpreting the Moore paper, and relevant since it is based on Jerne’s seminal, 40 year old “network theory”, which every schoolgirl knows is how the immune system functions. So what are we trying to explain? The loss of a cell-surface marker/receptor CD4 or the loss of a certain function that enables proper B cell functioning? What about the toxic effects, if any, of too many gp120-antibody immune complexes? Is there functional redundancy for “helper” T cells that a physician should also try to measure?

    It is worthy of note that “scientist” JP Moore, so nobly concerned about “the dangers of AIDS denialist sites in their capacity to mislead and hurt innocent, vulnerable people, particularly those infected with HIV who are seeking answers and information”, never specifies in a coherent manner what particular SCIENTIFIC ARGUMENTS on “denialist sites” are posing these dangers. Example, nowhere does he deal with looking at aberrant RNA processing in stressed cells as a reasonable physician’s conclusion after taking a detailed history of the sero-positive patient. This would be a health-promoting piece of advice to an HIVAb+ person, intended to reduce “antigenic” risk. Such a patient may actually be capable of accepting the diagnostic tests (without death-framing, of course) of the physician, learn about and evaluate stressors that can compromise health, act on this evaluation, and reverse the “HIV markers”. Even possible that a physician would not be robodoc, fighting the patient for taking this approach or pushing anti-virals as part of a “standardized” approach. Is “scientist” Moore not able to see that there’s room for a physician’s discretion in these matters, who – gasp – might even conclude that this particular patient is not at risk for a deadly viral infection based on the detailed history trumping the surrogate markers?

    But the main point: I am obliged to express gratitude to our gracious, but occasionally oversimplifying host, for bringing up the subject of the “env transcriptome” in the form of a paper on the subject of env’s most famous gene product: gp120, co-authored by the most fearsome of HIV warriors himself, John P Moore, a most determined professor from Cornell writing in a classic mister fix-it tone on the HIV vaccine problem. Why oh why, $200 billion later, the most studied “virus” in history, we know so much about the transcription of retroviral provirus by cellular DNA-RNA polymerase, but a viable anti-HIV vaccine still eludes this most dedicated research community.

    And we must applaud TS for this comment that the Moore paper is “typical of the HIV∫AIDS literature, which is something like a repository for trade secrets, written by insiders for insiders, which outsiders usually don’t try and gain access to, but if they do, they will find all kinds of revelations, which will turn their world upside down, by showing that HIV∫AIDS club members quite often show each other discoveries that they otherwise keep quiet, and make admissions they would never make in more public venues.”

    For sure, this is generally true, that nuggets that undermine the HIV hypothesis can be found in just about every research paper, since, of course, somewhere the truth has to be presented. However, it would not be worthy of NAR not to mention that this paper does not PROVE ANYTHING about so-called virions of HIV.

    For this is a review of gp120’s “other life”, it’s so-called existence apart from virions either anchored to a T-cell’s membrane or within plasma; a limited domain isolated for the exciting details of antigen-antibody reactions. And it gets very complicated with anti-idiotypes and yes, anti-anti-iditotypes that can make your head spin. Other “HIV proteins” isolated in cultures also can have toxic effects in vitro and form immune complexes in vivo.

    Gp120 comes to the cell surface when spliced mRNA env is transcribed and follows the pathway through the cellular secretory sytem, with synthesis of gp120 via ribosomes of the rough endoplastic reticulum. And here we get to the boring description of gp160 or gp120+gp41 => “the HIV envelope glycoprotein complex consists of trimers of noncovalently linked heterodimers” (means 2 structurally distinct – different from each other – “domains” of the assembled large protein molecule) “of an outer, receptor binding moiety gp120, anchored to a transmembrane protein gp41, which is involved in the fusion of the viral envelope with the cell membrane.” It is not stated in the Fig 1 text if this is on entry or exit from the cell but apparently it covers both.

    So this paper represents an unacknowledged contribution to “idiotypic network” theory, which appears to be a frontier of sorts for many “trade secrets” in the several combined disciplines that deal with immuno-molecular evolutionary phenomena. And indeed, dear readers, this paper has everything to do with our wonderful little tale of HTLV => HIV, from the other end, so-to-speak. We thank Moore as well, plus his co-author PJ Klasse (hereafter referred to as M&K) introducing us with this paper to the “cellular secretory pathway” of “surface unit” (SU) glycoproteins, gp120 being one example and MHC Class II receptor regions another. Both are anchored by transmembrane proteins, e.g. gp41 and have regions of hypervariable sequence space.

    But what is most important, can we make of the text, a brief for the point of view of Peter Duesberg on the effective antibody response expected to neutralize the “HIV” in vivo, as presumably documented by the in vitro studies reviewed by M&K. For alas, to all those long suffering readers of this tempestuous space, it is now my sad task to be the defender of scientific integrity and come to the aid of M&K, who would certainly tell us in no uncertain terms that this paper is not consistent with the idea of a “neutralized” or paralyzed HIV. But naturally the question that must follow: what on earth are we talking about in vivo when in vitro experiments are done with specific CONCENTRATED strains of “HIV-1”, most definitely NOT one?

    According to the data indicated by M&K and idiotypic network theory, activation of gp120 processes could be a way for T and B cells to deal with an antigen overload condition caused by conventional viral infections. Perhaps as an adaptive response to the “unhealthy blood” at least monomeric (

  11. MacDonald Says:

    Dear Nick Naylor,

    Thank you for a number of interesting err… hints.

    It has absolutely not escaped NAR readers’ attention that the paper in question is talking about ‘free’ gp120, whereas the elusive HI virion is supposed to keep its gp120 close to the body so to speak.

    However, just as you were about to tell us on Moore’s behalf what the significant difference might be between free and bound (to HIV) gp120, you broke off.

    So the question remains, does gp120 possess a greater ability to escape the body’s immune defences as part of the putative HIV package than it does on its own?

    In preparing your answer, you might want to consider once more Mr. Houston’s addtional information.

    Dr. Fauci and his colleague also pointed out that gp120 can act protectively as a partial vaccine: “Gp120 that had been produced in mammalian cell lines induced the highest level of neutralizing antibodies in laboratory assays that used HIV…” He also notes that “gp120 protected chimpanzees from HIV infection.” Fauci thus tends to confirm both Moore’s review and Truthseeker’s interpretation.

    HIV itself provides several proteins that elicit antibody responses and thus, as Truthseeker indicates, may be the best vaccine of all. Indeed, Cambridge University virologist Prof. Abraham Karpas has written: “The immune response to HIV can be compared to that of a live viral vaccine. It explains why most HIV-infected individuals remain well for many years.” (A. Karpas, Biological Reviews 79:911-933, 2004).

    As you note, the real thrust of the article is the in vivo versus in vitro distinction which Moore’s colleagues seem to be largely oblivious to.

    But one also wonders why the researchers are still looking – regardless how realistic the in vitro setting in which they are looking may or may not be – in this manner for direct cytopathic potential in the different HIV proteins singly:

    Some of these considerations apply, of course, to other studies of similar design that use high concentrations of other HIV-1 proteins, such as Tat and Vpr, in vitro, in the hope that this is relevant to pathogenesis. (Prof. J.P. Moore (my favourite quote for a variety of reasons))

    In this post Ho and Wei world, where HIV pathogenesis is the result 10-15 years down the line of a hyper-activated immunesystem, one wonders what it is going to prove even if the dilligent HIV researchers manage to kill T-cells in a test tube with a shotgun full of HIV-1 protein?

  12. MacDonald Says:

    PS. Nick Naylor is asked to accept that I’m asking my question from the traditional point of view of the existence of HIV as a real, exogenous entity, and NOT the alternative interpretation he proposes. From this perspective it is Nick Naylor forces me to frame the question so naively why – whether or not the existence of HIV-1 is demonstrated by Moore’s review – would its authors ”certainly tell us in no uncertain terms that this paper is not consistent with the idea of a “neutralized” or paralyzed HIV”?

    As I do not suppose the authors would tell us that the paper is not consistent with the existence of an exogenous entity called ‘HIV’, the only difference I can find is the one I assumed above, that the paper deals with the practice of sprinkling free gp120 on target cells, rather than whole HIV particles.

  13. fraorlando Says:

    Truthseeker, i was suspicious about your recommendation of the “voodoo effect of dire diagnosis” as a possible candidate for Illness in hiv positive people. However, in my search for answers, i stumbled upon this one: http://ajp.psychiatryonline.org/cgi/content/full/159/1/143

    So, according to Antoni et al. , HIV positive asymptomatic men receiving stress management training had a slight increase in CD4+ helper cells, whereas those not treated had a staggering decrease of 25 %(!), in the course of 1 year.

    Well, i must say i am less suspicious now…

  14. MacDonald Says:

    Orlando,

    This definitely looks interesting – and a very welcome change that the full text is freely available online.

    However, it would have been better if the subjects had been treatment-naive. It is stated that ”most of the men were not receiving combination therapy”. And although it is also stated that…

    ”these groups did not differ in HIV viral load or antiviral medications either before or after the intervention, suggesting that changes in immune system reconstitution over the subsequent year began from an even playing field of viral burden”,

    …it is very hard to believe that the subjects really started from, and especially remained on, the ”even playing field” during an entire year. It is, among other things, notoric that HIV/AIDS patients tend to cheat on their hard to tolerate drug regimens.

    A curious thing is that the 2 groups did not differ in viral load after treatment, although they differed dramatically in CD4 count. Non-correlation between viral load and CD4 count? Nahh can’t be…

    Another curious thing is that the drugs were performing SO badly, but that their effect/lack of effect was still completely cancelled out by the stress management.

    What is needed is a study that compares 4 large groups, one on drugs, one on stress management, one on both, one on nothing.

    Good luck with the grant application.

    BTW, what does non-AIDS-defining symptoms signify?

    HIV-infected gay or bisexual men between 18 and 55 years old with one or more non-AIDS-defining symptoms or a T-helper-inducer cell (CD3+CD4+) count of 200–700 cells/mm3

    You might want to look at another classic paper on AIDS voodoo, although from a different angle: Caspar Schmidt, The Group-Fantasy Origins of AIDS

    http://www.reviewingaids.org/awiki/index.php/Document:Group-Fantasy_Origins

  15. MacDonald Says:

    oops, that’s notorious, not notoric

  16. Michael Says:

    fraorlando, perhaps you should check out the following link. It is called AIDS AND THE VOODOO HEX
    By Matt Irwin Feb. 2002

    http://www.virusmyth.net/aids/data/mivoodoo.htm

    The following is a bit of his investigation:

    Severe, Chronic, Psychological Stress: A Painful and often Terminal Disease

    Severe, chronic psychological stress and social isolation can have health effects that are nearly identical to AIDS, especially when combined with physical stress or illness. Stress causes a state of immunodeficiency characterized by a reduction of the number of T-lymphocytes, with special targeting of CD4, helper T cells. There is also a reduced CD4:CD8 ratio, with a relative increase in CD8, suppressor/cytotoxic T cells (Antoni 1990, Bonneau 1993, Castle 1995, Herbert 1993, Kennedy 1988, Kiecolt-Glaser 1988, 1991, Laudenslager 1983, Pariante 1997, Stefanski 1998). Both of these immunological changes are considered characteristics specific to AIDS. Since being diagnosed with AIDS carries with it a high level of psychological stress and social isolation, low CD4 counts are likely caused, at least in part, by stress.

    A marked increase of the hormone cortisol, which is released during times of stress, appears to be one of the primary causes of these immune changes. Catecholamines like epinephrine, which are also released, have also been implicated but to a lesser degree. Multiple studies have found that people diagnosed HIV positive have chronically elevated cortisol levels (Azar 1993, Christeff 1988, 1992, Coodley 1994, Lewi 1995, Lortholary 1996, Membreno 1987, Norbiato 1996, Norbiato 1997, Nunez 1996, Verges 1989). It is important to note, however, that chronic stress can induce immune suppression even when cortisol and epinephrine are not elevated (Bonneau 1993, Keller 1983), so that the mechanisms by which stress affects health and immunity are not at all completely understood.

    Severe stress has also been shown to cause brain damage and neuronal atrophy, especially in the hippocampus, the area of the brain that controls learning and memory (Axelson 1993, Bremner 1995, Brooke 1994, Frol’kis 1994, Gold 1984, Gurvits 1996, Jensen 1982, Lopez 1998, Magarinos 1997, Sapolsky 1990, 1996, Sasuga 1997, Sheline 1996, Starkman 1992, Uno 1989,1994). This results in decreased mental function similar to what is often called “HIV dementia”. The most chilling research, however, is research that has demonstrated that severe social and psychological stress can cause a fatal wasting syndrome in animals, humans, and non-human primates that is very similar to AIDS (Benson 1997, Binik 1985, Campinha 1992, Cannon 1957, Cecchi 1984, Cohen 1988, Eastwell 1987, Golden 1977, Kaada 1989, Meador 1992, Milton 1973, Uno 1994).

    Being diagnosed HIV-positive is perhaps one of the greatest stressors one can imagine. Not only does it raise the constant and extreme fear of a relentless deterioration and death, but it also creates a social isolation that pervades all aspects of people’s lives. To make matters worse, many of the people diagnosed with AIDS already suffer from social isolation and rejection. Social isolation, alone, has been associated with a 100% to 200% increase in mortality in several large prospective studies, and the increase in mortality is equal to the increase associated with smoking (Berkman & Syme 1979, House 1988). The amount of psychological stress in people diagnosed HIV positive is likely to be much greater than the stress in the people in these studies.

  17. Nick Naylor Says:

    Mac Donald, as always you’ve raised fine points in response to the various gp120 phenomena, which some researchers consider to be a “down-regulator” of the “immune response”, i.e. many times a good thing if an individual is on the border of a so-called autoimmune problem. Since a so-called regulatory T cell is in the same business, here we can clearly point out a beneficial effect of this most notorious protein.

    Now, you say I leave off at the most interesting part – the reason alas – is that this “part’ resides in an individual’s difficult-to-briefly-describe overloaded idiotypic network and how it is regulating via molecular signals from antigens and reacting antibodies in plasma to the stage of cross reactions that include lymphocyte receptors, then signals from the cell’s membrane to the nucleus transcribing the “retroelements” known from cell-culturing to have certain defined triggers – the LTRs – which most definitely exist. The complexity, as revealed by an entire set of CD XX cells and “viral” nucleic acids, could be diagnostic of adaptive responses to the various pollutants and free radicals co-habitating in the patient’s body, and might include “HIV” proteins and its receptors but also go beyond. And maybe there ARE gag RNAs in plasma, indicative of the shift to excessive over-reactions with a potential for tissue damage by newly “misguided cells”, if the gag RNA is a surrogate for aberrant regulatory RNA’s causing havoc via exosome transfer to new cells.

  18. Nick Naylor Says:

    “As I do not suppose the authors would tell us that the paper is not consistent with the existence of an exogenous entity called ‘HIV’, the only difference I can find is the one I assumed above, that the paper deals with the practice of sprinkling free gp120 on target cells, rather than whole HIV particles.”

    Bravo, Macdonald, you have perfectly illustrated the “escape clause” one must use to stay in the HIV business. Do I think this is some kind of “conspiracy” or willed stupidity on the part of our best and brightest, who continue to pour forth such fine examples of science as we see in this review? Of course, sometimes at first it looks like such, but investigating further we encounter those places where the winks and nudges are artfully deployed. They are in such a specimen as we are currently examining and pointed out so well by our blog host.

    What’s important in HIV research is what is NOT known; this, of course is the holy grail of every paper and all funded authors are brilliant absolutely at the “Rumsfeld” strategy of finding those “known unkowns”, which always expand the territory simultaneously of the “unknown unknowns”.

    So when a smart-ass comes along and says, “You already have a DNA vaccine built-in with a retrovirus, what a waste of 200 billion dollars” … well … what can one expect as a response from those whose economic interests are tied to finding as many known unknowns as possible.

  19. MacDonald Says:

    Hmm Mr. Nick,

    As it was not possible to entice you back from the farthest metaphysical outposts of virology/immunology to a classical Duesbergian approach, would you not at least humor those of us less well founded than every school girl in the immune-regulatory function of gp120 and tell us by which healing mechanisms the heretofore most dreaded of all proteins becomes an over-loaded idiotypic network’s best friend?

    Or, since I’m not an initiate and therefore do not place myself in any grave danger of losing job and funding by cheapening the masonic trade secrets of virology (a metaphysical discipline per definition), in the plainest of words:

    What good is gp120 supposed to do us – and how?

  20. Truthseeker Says:

    Michael wrote: The most chilling research, however, is research that has demonstrated that severe social and psychological stress can cause a fatal wasting syndrome in animals, humans, and non-human primates that is very similar to AIDS (Benson 1997, Binik 1985, Campinha 1992, Cannon 1957, Cecchi 1984, Cohen 1988, Eastwell 1987, Golden 1977, Kaada 1989, Meador 1992, Milton 1973, Uno 1994).

    Being diagnosed HIV-positive is perhaps one of the greatest stressors one can imagine. Not only does it raise the constant and extreme fear of a relentless deterioration and death, but it also creates a social isolation that pervades all aspects of people’s lives.

    To make matters worse, many of the people diagnosed with AIDS already suffer from social isolation and rejection. Social isolation, alone, has been associated with a 100% to 200% increase in mortality in several large prospective studies, and the increase in mortality is equal to the increase associated with smoking (Berkman & Syme 1979, House 1988). The amount of psychological stress in people diagnosed HIV positive is likely to be much greater than the stress in the people in these studies.

    Good to highlight this factor, which is under recognized as a key factor in the health impact of AIDS presumably because it is hard to measure in studies.

    As a possibly minor additional factor, those who worry about illness are those more likely to respond to the suggestions of people like the Aaron Diamond AIDS Research Center, whose self-serving hand out cards read as follows:
    —————————————————————–
    IN THE LAST FEW WEEKS HAVE YOU:
    -had unprotected sexual activity, especially under the influence of alcohol and/or drugs?
    -shared needles and/or your works?
    -acquired a sexually transmitted infection?

    Do you have any of the following symptoms: Sore Throat, Headache, Joint Pain, Swollen Glands, Fever, Muscle Pain, Fatigue, Rash

    If you answered YES to any of these question & don’t know your HIV status…

    YOU DO NOT HAVE TO WAIT 2 TO 6 MONTHS TO BE TESTED FOR HIV TO BE ACCURATELY DIAGNOSED!!!

    Call ADARC for more information about free, confidential HIV viral load testing!!!

    Symptoms of acute or new HIV infection can occur anywhere from one to three weeks after infection with HIV.

    ADARC Proudly Support
    The Fight for Love and Life
    NYC’s LGBT PRIDE WEEK 2006

    All calls kept strictly confidential

    office:212-327-7260 * Cell: 646-258-9847

    elondono@adarc.org http://www.adarc.org
    ———————————–
    The Aaron Diamond
    AIDS Research Center
    —————————————————————–

    Comment: Fatigue after beer and sex? Get tested by David Ho’s research staff for the antibodies which signify that your body has defeated HIV, so that if you are missing said “positivity” you can be enjoined into the vaccine program on which the federal government and other sources have not yet expended enough billions, even though all concerned predict it may never happen (critics of the paradigm suggest that HIV itself is the best vaccine against HIV, since so far it has worked in every case, but their advice is scorned).

    If you run into David Ho do not mention the reason he won the Time Man of the Year cover in 1996, a research result which has since been exploded and abandoned even by the inner circle.

  21. Dan Says:

    IN THE LAST FEW WEEKS HAVE YOU:
    -had unprotected sexual activity, especially under the influence of alcohol and/or drugs?
    -shared needles and/or your works?
    -acquired a sexually transmitted infection?

    Do you have any of the following symptoms: Sore Throat, Headache, Joint Pain, Swollen Glands, Fever, Muscle Pain, Fatigue, Rash

    If you answered YES to any of these question & don’t know your HIV status…

    Then, yes, you could very well indeed have: sore throat, headache, joint pain, swollen glands, fever, muscle pain, fatigue or rash

    Amazing how they attempt to turn sex and a headache into AIDS.

    Sex and a headache. AIDS. Sure, why not?

  22. Michael Says:

    Aaron Diamond Research Center, headed up by the infamous fool Dr. David Ho, is part of the ACTG AIDS Drug Trials Group. They are paid by the pharmaceutical companies to the tune of $3000 to $10,000 and UP (whatever “and up” may mean), on a per patient, per drug, per trial basis. Many of the volunteers are on more than one drug and in more than one study, which means the research center can make quite a bundle from one person.

    As Marcia Angell, former editor of the New England Journal of Medicine points out, the drug trials serve TWO PURPOSES.

    One, to get patients onto a certain drug, from which the pharma company will cash in on either insurance companies or government paying for the lifelong prescription, and,

    Two, to get enough bodies on a new drug to get approval from the FDA to market the drug.

    As such, yes indeed, the AIDS drug trial groups want as many scared bunnies as possible to come in their doors with symptoms of sex and a headache, to be diagnosed as HIV positive by the highly flawed HIV tests, and from there it is easy to steer them into the drug trials, to keep the pharma funds rolling in.

    Another thing that all of these trial groups attempt to do, is to convince as many people as possible to submit to a very painful spinal tap, as the fluids are then sold to pharma companies for drug research.

    The volunteers are never told that their fluid is sold, nor are they ever told of the conflict of interest that is so obvious when the trials “study” group, such as Aaron Diamond Research Center is being paid by the drug companies.

  23. MacDonald Says:

    Actually the ambiguity in wording throws the widest possible net by asking people to come in if they’ve experienced any of the listed symptoms independently of sex and needle sharing.

    The incentive is greater if there’s a hit in both categories, behavioural and symptomatc, but since unprotected sex and ”acquired sexually transmitted infection”are separately listed it sends a signal that these transmissions, including HIV, can occur even under protected sex. Hence, by extension, flu symptoms or rashes in themselves are enough to trigger the fear factor.

    More importantly, it seems that PCR is now officially a diagnostic test functioning as its own gold standard since the ad very clearly states that one can be accurately diagnosed before a confirmatory antibody test can be used.

    ”YOU DO NOT HAVE TO WAIT 2 TO 6 MONTHS TO BE TESTED FOR HIV TO BE ACCURATELY DIAGNOSED”

    I recommend getting a test and if not ”accurately diagnosed” one way or the other, sue. It should make for a handsome out of court settlement – if they don’t make you sign some kind of bunny waiver first.

  24. Dan Says:

    Actually the ambiguity in wording throws the widest possible net by asking people to come in if they’ve experienced any of the listed symptoms independently of sex and needle sharing.

    You’re on the mark, MacDonald. I doubt that the wording (which doesn’t tie behaviors to symptoms) is an accident.

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