HIV Kills T cells...and doesn't need help to do it
A certain Clark Baker (one-time cop and marine by his own account - a good reason to brush up on my Karate for self defence if ever there was one...as it also appears his 'retirement' from the LAPD may have been spurred by an assault charge made by an immigrant) has started making noise and touting the same old disproven denialist lies (such as HIV is a harmless retrovirus, originally stated by Duesberg based on Duesberg's extensive personal experience working on HIV in the lab - ie none). Baker went one step further though. Taking advantage of what sounds like fundamental apathy in the society, he managed to infiltrate the Semmelweiss Society International (SSI) with other AIDS denialists, gain control of their bank account, and throw out the non-denialist board members. The SSI's remit was certainly honorable enough - to protect medical practitioners who are wrongfully accused of malpractise, but it has certainly lost its way. The takeover is all outlined in court documents filed against Baker which I have read. This infiltration certainly explains why the SSI saw fit to 'honor' Duesberg and Farber with whistle-blower awards.
The SSI website is now filled with the slightly hysterical, ill-informed, self-grandiosing propaganda that passes for AIDS denial these days.
The sad thing is that AIDS denial is no different from the Fiber One breakfast cereal. WTF I hear you say? Consider this:
The wife here is pissed, because "everyone knows" that foods high in fiber don't taste nice, therefore since Fiber One tastes nice, it can't have much fiber in it.
This is no different from Duesberg stating that "everyone knows" that retroviruses don't kill cells, and since HIV is a retrovirus, it can't kill cells.
The Fiber One commercials are funny. AIDS denial is resposible for killing hundreds of thousands of people.
Baker, on one of his recent rants, asks for proof that HIV kills T cells. Well, I pointed this out the AIDS denialists over a decade ago, but keeping up with the literature was never a strong point of AIDS denialism (denying the current science is what makes then denialists, after all). Incidentally this bit of research also explains a comment made by Montagnier (one of the original discoverers of HIV) where he states that a co-factor, along with HIV, may be responsible for AIDS - suggesting that HIV by itself might be relatively harmless. This, if it were true, wouldn't necessarily detract from the HIV->AIDS hypothesis, but it might have had an impact on how to treat or prevent AIDS, so it was well worth looking into.
Specifically, in this 1992 paper by Montagnier, they state that
Following infection of lymphoblastoid (CEM) or promonocytic (U937 and THP1) cell lines with HIV-1 cytopathic effect was observed only in association with mycoplasmal contamination. Moreover, HIV-1 infection of U937 cells after experimental inoculation with a human isolate of M. fermentans led to pronounced cell killing. We have verified that this effect is not merely an artifact caused by arginine and/or glucose depletion in the cell culture medium. These results confirm that mollicutes, in particular M. fermentans, are able to act synergistically with HIV-1 to kill infected cells in some in vitro systems.He had noticed that doxycycline could protect against HIV-induced cytotoxicity back in 1990. The mycoplasma detected here is a common problem in laboratory cell culture systems - they are notorious for upsetting experiments. I wonder if this notoriety came about because of results like this. It is not surprising that a mycoplasma, or some other co-factor, might be considered in AIDS causality, and the denialists are all over results like this as proof that HIV is harmless. But Montagnier only looked for cytopathic effect - i.e. what do the cells look like under the microscope. Look at this paper, from a couple of years afterwards. I'll post the abstract - basically they showed that the cell line Montagnier used (CEM in his original 1990 and followup 1992 paper) was not a pure line - it was partly CD4+ and partly CD4-. HIV can only infect CD4+ cells as that is what its envelope proteins (gp120 and gp41) bind to. It will come as no surprise to those who actually follow HIV science that in CEM lines, all the CD4+ cells get killed, but the CD4- cells grow to fill in the gaps (i.e. no cytopathic effect for Montagnier to observe).
This is a great example of how papers that apparently 'disprove' a hypothesis actually confirm it if you look at the science in greater detail.CEM cells were infected with three HIV-1 non syncytium-inducing (NSI) strains obtained from AIDS patients or seropositive individuals. The surviving cells were followed for several months in the persistently infected cultures designated 65870/CEM, 65871/CEM and 3929/CEM, and analyzed for virus expression using light and electron microscopy, immunofluorescence, reverse transcriptase assay, polymerase chain reaction amplification (PCR), nucleic acid hybridization and flow cytometry. The virus isolates induced relatively few syncytia and other cytopathic effects in the corresponding cell lines and the number of cells positive for virus expression never rose above 44%. Distinct peaks of antigen-positive cells were obtained, coincident with high levels of reverse transcriptase activity. The cultures were strongly resistant to superinfection by laboratory strain Lai, with the exception of 65870/CEM which expressed HIV antigens in up to 15% of the cells for a few days. However, cell lysis was minimal in all cases. After long-term cultivation of the three cultures, no antigen-positive cells were detected and no trace of virus expression could be observed. The remaining cells consisted entirely of CD4-negative cells. PCR analyses indicated that cells harboring a provirus were progressively eliminated from the cultures, leaving only virus-free cells. In this system, cells carrying a latent provirus survive for a limited period of time before virus activation induces cell lysis. These results suggest that at least three types of cells exist in the CEM cell line: CD4-positive cells which are rapidly killed by the virus, a second type harboring a latent viral genome after the infection and which grow normally until activation of the resident genome by external or internal signal(s), and a third type which represents rare CD4-negative cells present in the initial CEM population and which are selected for by the NSI isolates. This is the first study documenting specific interactions between NSI strains of HIV-1 and distinct subpopulations of CEM cells grown as a single cell culture.
To wrap up the story, it's well known that monocytes/macrophages like the U937 and THP-1 lines are responsible for longterm infection with HIV, the "reservoir" of infection that is hard to kill. But this makes sense - HIV doesn't deplete CD4+ macrophages to cause AIDS, so HIV wouldn't be expected to kill monocyte cell lines in the lab...unless perhaps the cultures were contaminated with mycoplasma... Maybe Duesberg was half-right.
In any case, just as Fiber One is a tasty source of fiber, HIV kills cells.
This whole story is a great example of why AIDS denialism has moved from a legitimate question-asking exercise, through inexplicable stubborness and willfull ignorance, to downright evil. When AIDS denial is touted by homophobic, ignorant, arrogant people who (allegedly) lie and steal in order to further their devastating agenda, then it's really fallen about as far as it can go.
Bennett
Disclaimer: I have never bought Fiber One, nor do I endorse them. I have however worked with HIV in the lab in short and long-term culture systems and witnessed its cytopathic effect. I use the word "allegedly"above as Baker is so far accussed, but not proven, to be a homophobic, racist, ignorant, arrogant, liar and thief. However, anyone who calls AIDS patients "a small group of promiscuous, addicted, nitrite-huffing, gonorrheal and syphilitic bath house veterans" probably needs no further said of them.
Lemaitre M. Guetard D. Henin Y. Montagnier L. Zerial A. Research in Virology. 141(1):5-16, 1990 Jan-Feb Protective activity of tetracycline analogs against the cytopathic effect of the human immunodeficiency viruses in CEM cells.
M Lemaître, Y Henin, F Destouesse, C Ferrieux, L Montagnier, and A Blanchard
Infect Immun. 1992 March; 60(3) 742–748. Role of mycoplasma infection in the cytopathic effect induced by human immunodeficiency virus type 1 in infected cell lines.
Yelle et al Arch Virol 1994;139(1-2):155-72 "Analysis of long- term viral expression in CEM cells persistently infected with non syncytium-inducing HIV-1 strains.
posted by Bennett at 8:45 AM
18 Comments:
Great post.
Clark Baker’s statements are undeniably homophobic. That is, except to an AIDS Denialist. The verbose Gay AIDS Denialist Michael Geiger has said Clark Baker “has always been respectful and decent, and I have not seen evidence to believe he is homophobic, but I have clearly seen just the opposite, as he and his wife have many gay friends who hold him in high regard.” He said Baker did not mean any offence by referring to AIDS being caused by a Gay Lifestyle.
There are apparently no limits to denial among AIDS Denialists.
Seth Kalichman
http://denyingaids.blogspot.com
Bennett,
So glad you are back! See, Clark Baker is not all bad, as he inspired you to get back to blogging. It is so funny to me to read Baker's blogs, especially when he gets into science in any way, as he proves what a dolt he is.
Your post here is great, however, for Baker et. al. to understand it, perhaps you should provide links to clarify the meanings for them regarding cytopathic effect, syncytia, mollicutes (I did not know this one...I knew mycoplasma did not have cell walls, but did not know that mycoplasma ARE mollicutes!) etc.
For another great laugh at Baker's stupidity, please see his blog about HIV Meds in general, and Sustiva in particular, where Baker tries to make us believe that all HIV Meds are addictive and are not only just like cocaine, heroine and meth, but are also just like anti-depressant SSRI's! Three totally different classes of drugs! Then read my explaination where I prove that everything Baker writes is 100% wrong using the very links Baker supplies! I am actually quite proud of this one:
http://dissidents4dumbees.blogspot.com/2009/05/clark-baker-is-scientifically.html
Again, good to have you back!
JTD
Seth, you are correct. As a gay man who personally witnessed the very history of which you speak, I do not see those words written by Clark as homophobic.
I would like to point out that from the late 70's and all through the 80's and into the 90's, I myself had personally witnessed the gay party scene and early in my own youth, I nearly got caught up in it myself.
In 1978 alone, in my late teens, I myself had sniffed poppers, coke, smoked a lot of pot, did acid and had gone several times to bathhouses, and the results for me where a couple of cases of crabs, syph, and gono. So I assure you that it is quite accurate when someone speaks of some who got very caught up in the early gay scene as:
"a small group of promiscuous, addicted, nitrite-huffing, gonorrheal and syphilitic bath house veterans"
As for myself, for a very brief period in time, although I did not get addicted, I was one of the above myself.
The truth may hurt a bit as I myself reflect upon it, but there is nothing homophobic about pointing out the truth, as after all, it is still the truth.
Once again I have to point out the elementary and the basic, which you Dr Bennett appear to run right by in your zeal to go after Clark Baker and Peter Duesberg.
I see Mr Kalichman has responded. Hopefully you sir can answer a charge made against you. I’ve been told that you will not post comments on your blog regarding scientific objections to alleged fact of all-powerful immuno-destructive virus (APIDV) “assembling itself” into a contagious form from retroviral genes and cellular transcription factors in primates. The argument from APIDV reduces to patient has HIV markers, with inevitable collapse of the patient’s immune system reducing to disappearance of the CD4 t-cell marker. This is supposedly an explanation for all the diseases that constitute AID syndrome.
Can you two handle my objections to what you call irrefutable evidence of HIV killing CD4 cells IN VIVO?
Apparently, “denialists” are those who object in any way to the absolute truth of these reductions. It follows that they are ethically as well as scientifically challenged for raising their objections because even this process somehow “costs lives”. Of course, the empirical basis of this last part doesn’t exist but here we get to the realm of ingenious psychology, eh Mr Kalichman. The more one denies, the more proof we have of a seriously disturbed individual? Why? Because of the disregard for human life, of course.
Thus we “ban” denialists and restrict their speech?
Would you care to confirm or deny such charges in this forum?
Maybe take the rest of this seriously?
So what if in 1984 the prototype high kinetic RT rates of cell cultured HTLV III/LAV were an artifact?
What if complete dimeric genomes – a measurement that would imply hyperactive replication in vivo - have never been demonstrated in AIDS patients? Should they ALWAYS be below detection threshold?
I’m assuming these questions are intriguing enough to my ol’ pal and his “info portal”, so let’s get it on starting with the “usual stuff” – has Dr Bennett shown “invincible ignorance” when it comes to the subject of Peter Duesberg? Dr Duesberg apparently is not qualified to comment on HIV because it’s so much more “complex” than “acutely transforming” retroviruses. But after all my years of reading retroviral papers (even more than the ones Brian Foley has directed me to), I have no idea what Dr Bennett is talking about. Maybe I’m clueless on bright high school students, but the comprehension that acutely transforming retroviruses are so because onc genes replace env genes should be within their grasp.
END PART ONE
Regards,
Gene Semon
And Dr Bennett, you seem to be unaware of a Duesberg and Goodrich paper on well-documented retroviral template switching published circa 1990 (not a review). It reports on experiments to clarify open questions on retroviral recombination, which BTW can change a lentivirus to an acutely transforming retrovirus. So what? Surely Dr Bennett you’re not asserting that recombination doesn’t occur in HIV strains, but when I read what you put up here it looks like HIV is simply a monolith, kind of a world apart from all other retroviruses. This is NOT justified, especially considering kinetics and thermochemistry, and from experimental data IMO.
A complete “life cycle” can be framed from provirus to provirus, (Temin’s alternative definition) and here one can see different “biological parents” (first set of cellularly transcribed proviruses) and “recombined children” (second set of proviruses integrated in another cell). It is likely that recombination occurs during the reverse transcriptase step.
Different HIV cloned genomes produce particles that have different biological properties, that’s what HIV researchers have concluded. This suggests a different frame, can a null hypothesis on matter of CD4 killing be reasonable? According to the “other guys”(1) frame, there are no “impossibility barriers” when it comes to “riboswitches” and the “fluid genome”. For a “wild type” human retrovirus, a new “strain” can be produced in one reverse transcription step depending on the available concentration of ORF HERV RNA templates. The human genome can obviously be the source of different env proteins. They in turn control the “cytopathic effect” - in culture referred to as “syncytium inducing”. There are non-syncytium inducing HI retroviruses. Thus one cannot rule out, if we’re proceeding in a scientific manner, a combined HIV/HERV strain where the HERV ORF provides a syncytium inducing env protein in vitro. Or there would more likely be an “attenuating” effect in vivo as the “survival disadvantage” of cell killing is “bred out” by an immune system that cell-cultures don’t have.
And I’m not even considering the documented (2) intracellular retroviral restriction factors at this stage of the discussion.
Additionally, since “blog debates” started for me in Jan, 2005, I’ve come across several
“qualified HIV experimenters”(3) who ignored human LINE ORF2 in their postings on reverse transcriptase from the human genome. This has great significance IMO for discussions on the subject of retroviruses when these learned individuals do not know that LINEs can retrotranspose HERV genes (technically pseudogenes when reinserted by L1 elements).
END PART TWO
Regards,
Gene Semon
Thus, is it unreasonable given mixed results in “securing” retroviruses from organisms to cell cultures to at least provisionally accept a null hypothesis, ESPECIALLY considering the published experiments on HIV?
So let’s not speculate on what Duesberg does or doesn’t know. Or how many uncritical inferences his “strict followers” make. I’m more interested in you guys now, the larger implications of “truther” doctrines.
I say let’s provisionally ignore what “denialists” say, and take a fresh look: is it reasonable for authorities, the “deciders”, to judge the “ethics” differently than truther doctrine argues for?
Thus and firstly, it’s most important to look behind the “risk assessment”(4) numbers, the “lives saved” or “lives lost” that come from mathematical models. These are NOT the same thing, my dear Dr Bennett, as empirical data or “statistics” as reported by mainstream journalists. And after all, empiricism sensu strictu is the only basis for “science” as I read Mr Kalichman.
Here we can introduce famous objections from oh so many philosophers, but this is not the time for all THAT.
Let’s simplify in light of technical points above: if science represents real knowledge, it can only come via critical thinking. It follows that when we let others do our thinking for us, we are not practicing science.
So taking a fresh look at the data from HIV experiments lo these many years and (gasp), its even within reason to provisionally accept a null hypothesis* on the association of HIV markers with CD4 cells IN VIVO.
As far as wider implications that so interest me, it seems to follow that practice of science according to truthers gets reduced to some kind of assembly line. Like insects or machines, in the brave new world we are supposed to “ignore” larger patterns that may emerge from our minds in order to “progress”. Then, just like within a pharmaceutical company, by an amazing coincidence, all knowledge must be tightly compartmentalized or it’s not “true”. So corporations control who become “scientists”, since only “qualified people” with “hyperspecialized genius” in virology, etc, get hired. Perhaps but not necessarily intellectually stunted in political arena, also to the good from bosses standpoint ...
And thus as Orwell predicted, there are unthinkable criticisms of the biotech enterprise – no available language - at least from those who want to stay employed: don’t go where the denialists go - the clear message.
And “science” can no longer discern larger patterns or be interdisciplinary or come up with new grand theories other than “string theory”. At least that looks like the “vision” of certain self appointed “science guardians”, clearly in a heightened state of alarm over lay people seeing “unauthorized patterns”. (See Scientific American, July, 2009, pg 36 – the “Skeptic”.)
Apologies for no references but will put them up for technical points if there’s to be another round.
Regards,
Gene Semon
1. Kind of a grab bag of retrogenomics, “genomic tag”, RNA structuralists, RNA regulation, etc. researchers,
2. Same ones it turns out by HERV and HIV investigators
3. Or so what! I’m not doubting their abilities to read scintillation counters or spin the centrifuge for the right amount of time. The point is, where do we wind up when we take seriously such a standard as Dr Bennett proposes to judge a Peter Duesberg?
4. The fun and games of my past professional life
*yes, even at this “late date” :o)
END PART III
Regards,
Gene
Gene,
I don't forbid comments - what I will not do is engage in fruitless debate. There are enough websites out there for AIDS denialists to do that without me supplying another one.
If you can (a) find the HIV genome in the human genome and (b) explain how, if it is in fragments, how and why it gets put together into a coherent, replication competent exogenous retrovirus, then you might have case.
But I doubt you can do that, because I have tried to look for such sequences myself, and they aren't there.
Because HIV isn't an endogneous retroelement, or even a composition of such parts.
I am well aware that HIV recombines - my PhD thesis was to investigate the mechanisms differentiating HIV-1 (promiscious genome packager) to HIV-2 (selective genome packager). HIV genome dimerization, packaging and Gag protein transcription are intimately linked - and dimerization is of course why HIV can recombine at all.
Your idea is a nice one, but very easily disproved - and it has been over and over again. You can do it for yourself using the publicly available sequences in GenBank. The LINE elements and HERV's aren't being ignored because of a kind of selective ignorance, but because they are not HIV.
The "env" gene of HERV-K or the Syncytin gene is no more like the "env" gene of HIV than the "leg" of a hippopotamus is like the "leg" of a cat. Both are clearly legs, both will contain the same bony elements, muscles, arteries and nerves - in the same way as env proteins will have similar loops and steps and domains - but at a fundamental level they are clearly distinct. You can test this graphically using the BLAST algorithms freely available online for protein/genetic comparisons.
I have just run a genetic comparison of HIV-1 (accession k03455) and HERV K (accession U07856.1). Result: no significant similarity found.
On the other hand, HIV-1 versus SIVcpz (from chimps, accession AF115393.1) gives a nice linear match for most (77% identical) of the genome.
The persistence of AIDS denialists in trying to make something of these genetic elements is the true selective ignorance. It's also somewhat arrogant to consider that they have somehow thought of something that those who work with these retroelements on a daily basis haven't already considered and ruled out.
Bennett
Dr Bennett,
OK fine you can have the last word here obviously.
But allow me to retort ...
The taxonomic problem or "theory of ordering" considers IMO either retroviral genes as repetitive DNA elements or versus "isolating" RNA transcripts labeled "exogenous" based on defined protocols of extraction from cell cultures which sum total of protocols may itself cause mixing of genetic "fragments" or "artifacts".
So it is also known that APOBEC family of proteins are general "restriction factors" with "special relationships" to both HIVs and HERVs. Thus some have crazy idea known currently as the "need for a HERV transcriptome project" which takes head on as I see it the exogenous versus endogenous "impossibility barrier", resolving perhaps the many (some believe arbitrary) ways one defines what HIV markers represent.
Additionally, I've found a "star phylogeny" (means "unrooted" - no direction of evolution indicated), according to phylogenetic investigations into HIV-1, better I think than irrelevant animal limb analogy*, i.e. meaningless phylogenetic comparisons with vertebrate life forms when specifying the function of env genes. The syncytium inducing conserved residues may show up in any retrovirus. Dr Bennett, you leap for the higher animal analogy and miss here methinks that all retroviral nondefective envs code for transmembrane and surface unit proteins.
Thus HERVs and HIVs are (provisionally) overlapping sets given the "continuous spectrum of genetic variants" that have the potential to produce particles with "different biological properties" claimed not by denialists but by HIV researchers to represent the set HIV-1 (plural).
So which HIV isn't like which HERV is a meaningless question given current knowledge of human retroviruses. Not worthy of the label empiricism either is looking at what's programmed in computers which obviously cannot represent the polymorphisms of HERVs in human population.
You said, "If you can (a) find the HIV genome in the human genome and (b) explain how, if it is in fragments, how and why it gets put together into a coherent, replication competent exogenous retrovirus, then you might have case."
I've dealt with (a) and (b) has been done by Howard Temin in his publications on the protovirus hypothesis and retroviral recombination. You want me to “make a case”, but just considering "directed mutation" guy John Cairn's published support of the protovirus hypothesis - from transposable elements to budding particles - plus what's been published since then, I must reverse the issue. Why you can't even come up with a model of "complementative transcriptions" that would "feed forward" from the genome to budding particles is a deep mystery to me. It reminds me of that famous debate: is it design or evolution of the bacterial flagellum?
So it must be true that Dembski's part of the neo-Nazi conspiracy?
:o)
Of course Dr Bennett you and Mr Kalichman don't have to respond to my questions, but really I'm just trying to help here because I think Mr Kalichman wants to set the record straight, so he can be taken seriously with his thesis and all that ...
Kindest regards, luv hugs and kisses,
Gene
*You realize of course that the complexity of hox genes further reduces the power of your analogy. Why? The very case I'm making is for defining retroviruses by "their" complex cellular on and off switches, complex transcription unit (CTU).
Gene
I let you through mostly to illustrate to the reader what pseudoscience looks like.
I can certainly grasp the concept of a piecemeal mish mash of genetic elements coming together to form an exogenous budding viral particle, but it's highly unlikely (especially in the sense that no such fragments have been found!) Occams Razor argues that if you've found a full-length genomic transcript of a retrovirus, and it by itself explains all the replication steps necessary to self-propagate, then there is no reason to invoke a mythical gestalt of other elements to cause it.
I think it is you who have missed the point. I did not invoke the higher order mammalian contrast to jump ahead. I used the analogy to directly compare the transmembrane and surface units with (say) the femur and tibia of a mammalian leg. SU and TM units are recognizable as such, same as femurs are recognizable as such, but a hippo femur looks different a cat femur - same as a HERV env looks different from an HIV env.
Just because you know of a number of env sequence in the human genome, it does not follow that these env's have anything whatsoever to do with HIV - not least because none of them look like HIV env.
You have failed entirely to deal with the idea of HIV sequence in the genome.
Explain why, when a hybridzation experiment such as a northern or southern blot is performed using HIV sequences, such sequences do not bind to normal cells...? They only bind to cells that contain the full length genome, introduced by transfection or infection. This can be done in the lab or from real human hosts! If HIV sequences were present in the genome then the sequences would be found using such techniques. In fact, the absence of HIV in the human genome allows for negative controls in experiments.
I'm not arguing the case based on some theoretical concept of difficulty, or some database entries, but on the sheer inability of anyone to find HIV in the normal human DNA using any kind of technique - whether targeting DNA or RNA, PCR or probes.
This isn't even an issue that needs to be addressed, because it has been, and is still being disproven day after day in HIV labs around the world in their negative controls!
AIDS denialists of course state (falsely) that such controls do not exist. Unfortunately for them the scientific literature clearly states otherwise...
Dr Bennett,
Thank you for allowing continuation of this dialogue. I appreciate your considered responses.
But I will continue to insist that YOU fail to make a case that what I'm posting here is pseudoscience.
For one thing, as I'm reading it anyway, you continue to mix up various HIV markers with the thing itself. This was my original point re failure to detect the complete dimeric genome - which bands at 70S on the Svedberg scale - in AIDS patients. Where is the evidence for hyperactive replication in vivo? Clearly, if you want to invoke "development" there's no demonstrated "cytopathic variant", with all its necessary "limbs", wreaking viral mayhem unless there's evidence for it directly from patients.
Nor did Gallo, using hybridization probes of his HTLV III/LAV, fulfill Koch's postulates, detecting proviral DNA in only 15% of AIDS patients in 1984. And there's pprobably no way you can prove that some of those probes weren't cross reacting with the then unknown HERVs.
Additionally, it's also true that HIV primers have indeed picked up endogenous sequences.*
So here I must pause in recognition of your hospitality and the fact that I'm "running up a tab" re references to be put up.
May I suggest, regardless of the attempts at clarification using analogies to higher life forms, you still haven't gotten it re the significance of gp120, which for many HIV researchers appears to be the handy "stand-in" for HIV. Check out Ascher and Sheppard's response to Ho and Wei in Nature 1995 to see what I mean.
If it's "all (or mostly) in the gp120**" (plus another "accessory protein"** in tandem) effecting the disappearance of the CD4 marker, it is NOT accurate to simply call it a HERV env gene. So can you exclude recombination break points or hot spots WITHIN HERV env ORFs that can produce gp 120 and gp41, which some might call "paraproteins", i.e. not "normally" coded by human genome? But a caveat here as well, we simply don't know if gp160 is directly coded or not by some human genomes.
All this takes us very far from lytic cell killing, not in the "developmental program" of any retrovirus, it seems to me.
Wasn't Gallo et al's "unique cytopathic variant" model of cell-killing rejected by the likes of Simon Wain Hobson?
So once again, with all due respect, it looks to me that you prefer to grab at what's "handy", e.g. continuing to imply that HIV is singular, and labeling as pseudoscience what seems to be obvious, i.e. the plurality of different HIVs. This greatly disappoints me Dr Bennett; your failure to see that this is not resolvable by a "crucial experiment", or set of same.
Best regards,
Gene
*Sure, here's where some data back-up from me would be in order :o)
** presumably from Montagnier's 3' half of LAV
Good lord sir, you make it difficult to parse what you write.
I'm sorry, but to state "the moon is made of cheese" and then leave it up to someone else to prove that's a false statement is ludicrous - that's basically what you are saying when you say that it is up to me to prove that what you are saying is pseudoscience...
I apologise for the fact that you felt the need to write again in case I was censoring you. I do in fact have a job and a family, and blog in my spare time - and this is one reason why AIDSmyth is not the best forum for denialists to discuss their agenda on. If I take some time to moderate comments, then so be it.
I like it that way :o)
Why focus on Gallo? Ho and others have found HIV DNA in 100% of AIDS patients and 0% of seronegatives...no cross-reactions there.
Henry Ford couldn't get the model T to go 100mph, so I guess Nascar drivers don't exist!
I certainly do not imply that HIV is singular - but even among the pseudospecies and clade variants, enough similarities exist at the genetic level to link them together, and distinguish them from anything else.
This is absolutely resolvable by experimentation, and has been to the satisfaction of sensible virologists worldwide.
You SOUND superficially very knowledgeable, but as someone who is very familiar with HIV and AIDS science, and AIDS denialism/pseudoscience, it's clear to me that your UNDERSTANDING of molecular virology is wafer thin.
There are thousands of experiments in the literature that would fall apart if HIV were NOT an exogenous retrovirus - something that people like the Perth Group (and presumably yourself) seem either to conveniently forget or purposefully ignore.
For a time I entertained the idea that HIV-1 was a product of a 3' recombination even between SIVcpz and either an endogenous RV or another exogenous RV (harmless, and therefore undiscovered to date). That might still prove to be the case, but it doesn't detract from HIV as an exogenous RV right now, nor from the HIV->AIDS paradigm - especially with the clinical benefits of preventing HIV transmission and anti-HIV therapies proven time and time again.
AIDS denialism should have died with the arrival of the protease inhibitors and truly effective life-prolonging regimens. The fact that it didn't is, well, denial.
Dr. Bennett,
I am little disappointed that you have let Gene lead you astray in this manner. And I am positively terrified that, with all the fine technical points you are making about HIV sequences in the human genome, and what northern/southern blot pick up and don't pick up, you have resorted, as your knock-out argument, to not-so-scientific canard about the clinical efficacy of the drugs.
Perhaps you are just trying to bring the discussion to a level where even Seth Kalichman can sort of follow what's going on, but we are merely diverting ourselves by going down THAT path if, so, if you don't mind, I'd like to return to the topic of your post - Cell-killing by HIV I mean, not the silly ad hominem stuff. Why not leave politics to the politicians and give us the benefit of your scientific genius instead? It is clearly where you real talent lies.
So, to cut to the chase, what in your opinion is HIV's main method of cell-killing in vivo?
What is/are HIV's method(s) of cell-killing in vitro?
On the background of your answer to the above, what is the relevance of the in vitro observations you write about above?
Bennett,
I freely admit that I do not know much about the genetics of HIV that this Gene Semon is going on about, but he did come across to me as similar to the character Damon Wayans played "In Living Color" the convict "Oswald Bates" who spoke with an incredible vocabulary, but not correctly!
Also, I may be confused, but from the get~go, Gene chimed in about
CD4 cells being killed IN~VIVO, but the cytopathic effect you were describing was In~Vitro, was it not?
Anyway, it truly does show when someone knows what the are talking about in very difficult, scientific conversations, as you came across as knowing what you were saying. Mr. Semon, did seem a bit disjointed. And with no links to back up his claims, he seems even more dubious, at best.
Thanks for keeping things legit.
JTD
Thank you Doctor Bennett for not censoring me.
I promise to respond to your points; they are well taken.
Again, notwithstanding difficulties in my "compressive prose", which I understand can be mistaken for postmodern jive; it's going to take some real substance to hold the line on "your kinetics argument": HIV not demonstrated to replicate in vivo hyperactively at sufficient "strength" to kill CD4 cells => pseudoscience.
Hard kinetic data, that's what I'm talking about.
Best regards,
Gene
So, three comments in a row all pointing out the fact that in vitro data doesn't always correlate with in vivo data.
However, that wasn't the point of my post. My point was simply to show that the denialist mantra that HIV is non-cytotoxic is false.
I've said for a very long time that HIV doesn't need to be cytopathic to the same extent in vivo. You can read a couple of comprehensive posts of mine here.
http://aidsmyth.blogspot.com/2004/08/refutation-to-some-of-duesbergs-stuff.html
http://aidsmyth.blogspot.com/2004/10/latest-bmj-rebuttal.html
As you can tell, and as many Denialists are fond of touting, the old "Tap and Drain" model of AIDS pathogenesis has been discredited: that was basically that HIV replication was so high that it overwhelmed the immune system (opened the drain) such that the replacements (the tap) couldn't keep up.
However, the data on normal T cell replication rates suggested that the tap could indeed keep up. So then what...?
So then it was shown that during HIV infection the tap is turned off - basically, HIV screws with T cell replacement from the thymus - so not only is there increased cell death, there is decreased cell replacement. And many of the dying cells aren't even HIV infected! T cells die as part of the normal immune response (if they didn't you'd be overwhelmed with a leukemia-like reaction after every little cough and cold) so chronic HIV infection causes chronic overactivity of the immune system and rapid T cell turnover. But that turnover leads to decreased cell numbers if the normal T cell replacement is defective - as it is in HIV infection.
We don't really know WHY the replacement rates are so messed up - but we know that they are, and we know that treating HIV corrects those defects (and it isn't increased T cell survival that leads to a long-term increase in CD4 T cell counts, it's an increased replacement rate).
This is ten-year old data.
So I'm not arguing the case that "HIV causes AIDS because it's cytotoxic" - I'm saying that "The denialists are lying when they say that HIV isn't cytotoxic, and in any case it doesn't have to be to cause AIDS".
The narrow-minded thinking that expects only a single reason why CD4 T cell numbers might drop, and the persistence of that thinking in the face of better, alternative explanations, is why the term 'denialist' is so appropriate.
The kinetic data Gene desires in laid out in such papers as those I reference in the links above.
As Duesberg said back in 1992 AIDS must:
"(4) Coincides with a microbe that lyses or renders nonfunctional more cells than the host can spare or regenerate. "
but he ignores the other possibilities such as:
And/Or hinders the regeneration of those cells. HIV reduces the CD4 cell survival time and hinders replacement from the thymus. The effect of HIV is reversed by antiviral therapies. (Duoek el al: Nature 1998, Hellerstein et al Nature 1999) HIV is cytotoxic (Yelle et al: Archives of Virology 1994, Rasheed et al: Virology 1996, ), and may be immunosuppressive even in the absence of active infection (Diamond et al: J immunology 1988, Weinhold et a l: J immunology 1989, Daniel et al: Clinical Experimental Immunology 1993, Liegler and Stites: J AIDS 1994, Theodore et al: J AIDS 1994, Schols and De Clercq: J Virol 1996, etc - I haven't even started on the accessory proteins of HIV). The immune response to the virus will, of course, attack the immune system itself. As such the number of cells the virus actually kills by infection need not be the limit of the immune dysregulation. Direct in vivo evidence of this lack of correlation between cytotoxicity and immune suppression exists in chimps (Wantanabe et al: J Virology 1991)."
I reposted that rebuttal back in 2004. I seems as if Gene (and others who are interested) ought to start by reading some of the older posts on this site, where their questions are already answered.
Bennett,
I love that you admit that science does not know everything about CD4 death by HIV! Science always acknowledges when something is not yet proven or understood, and yet the denialists jump on this admission as a weakness!
I just do not understand their rationale (of course, denialists would not be denialists without a dubious rationale). However, when science admits not knowing certain facts, this is perfect proof of the legitimacy of science. We do not make up answers when they have not been proven! This is not a weakness, but a strength.
Too bad the denialists act as if they have the answer for everything! If they could admit a weakness now and again, they might just seem to be a wee bit human!
JTD
On the Endogenous Issue:
Fact: HIV has been shown to be exogenous throughout 20+ years of research.
An endogenous retrovirus is one whose genetic material has been incorporated into that of the host. This happens when the genome of the virus incorporates itself into the chromosome of the host's sex cell (sperm or egg) – or its progenitor – and thus, upon fertilization becomes part of the normal genome found in every cell in the body of the host. Over time, the endogenous retroviral genome usually accumulates deleterious mutations rendering it incapable of productive infection. One myth used by denialists is that HIV is one of these endogenous retroviruses. However, several lines of evidence from the published scientific literature refute this claim, and prove that it is an exogenous virus, found only in CD4+ T-cells and a few other CD4+ cell types (such as macrophages) and not found in most other host cells.
Early evidence:
In the very first publication regarding the identification of HIV, Dr. Luc Montagnier described several experiments showing that HIV was exogenous. The controls used in his co-culture experiments, for example, did not produce a reverse transcriptase signal, only those cells exposed to infected patient lymphocytes. This indicates that the signal did not originate from the genome of the uninfected donor cells. The RT signal (and thus the virus) was able to be passed on to other uninfected lymphocyte cultures and resulted in a similar RT signal pattern. This passing on of the virus is another line of evidence that HIV is unlikely to be endogenous [1].
Southern Blots:
The southern blot is a method for probing for the presence of a specific DNA sequence within a DNA sample. In southern blot hybridization, a small segment of single-stranded DNA is hybridized to genomic DNA. There is nothing in the human genome that hybridizes at reasonable stringency levels (i.e. the specificity of the test) to probes made from HIV-1 or HIV-2 proviral genomes[2]. One study did find two very short sequences (192bp and ~30bp) with some similarity (<60% and 95% respectively) to parts of the HIV genome. However, these two sequences were detected only under very low stringency (low specificity) and no other sequences with similarity to HIV were found [3].
PCR:
In experiments using PCR (another method for detecting specific genetic sequences) in infected patients’ lymphocytes, PCR detects HIV in only a fraction of the infected donor’s T-Cells [4]. This alone is enough to demonstrate that HIV cannot be endogenous. An endogenous virus, by virtue of its past integration in host germ cells, would be detectable in all nucleated cells of the host. In other experiments, HIV DNA was found in the lymphocytes of patients but only very rarely in sperm cells [5]. The absence of HIV DNA from certain cell types in patients again refutes the idea that HIV is endogenous.
(continued)
The Genome Projects:
The genome projects have been a valuable tool in the field of genetics and also refute the idea that HIV is endogenous. At the time this article was being written, only two examples existed in the scientific literature of endogenous lentiviruses in mammals: one in rabbits and one in lemurs [6][7]. All sequenced primate genomes (including several human genomes) show no endogenous lentiviral genomes.
Common Sense:
Some common sense combined with a brief look at infections would likewise indicate that HIV is not endogenous. If it were endogenous, sequences would be most similar between family members and most different between distantly related individuals. However, this is not the case. Europeans of non-West African descent have been identified with HIV-2 infection, despite HIV-2 being predominantly found in West Africa [8]. Conversely, many Africans have been infected by HIV-1. If one claims that HIV is endogenous, one therefore also claims that West Africans with HIV-2 infections are more closely related to non-West African Europeans with HIV-2 infection than they are to their HIV-1 infected countrymen. This is simply absurd.
References
1. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vézinet-Brun F, Rouzioux C, Rozenbaum W, Montagnier L. Science. 1983 May 20;220(4599):868-71. PMID: 6189183
2. Characterization of a continuous T-cell line susceptible to the cytopathic effects of the acquired immunodeficiency syndrome (AIDS)-associated retrovirus. Folks T, Benn S, Rabson A, Theodore T, Hoggan MD, Martin M, Lightfoote M, Sell K. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539-43. PMID: 2989831
3. Novel human endogenous sequences related to human immunodeficiency virus type 1. Horwitz MS, Boyce-Jacino MT, Faras AJ. J Virol. 1992 Apr;66(4):2170-9. PMID: 1548756
4. Sensitive detection of HIV DNA in T4 lymphocytes of infected individuals by polymerase chain reaction.
Hsia K, Spector SA; International Conference on AIDS. Int Conf AIDS. 1990 Jun 20-23; 6: 160
5. HIV-particles in spermatozoa of patients with AIDS and their transfer into the oocyte. Baccetti B, Benedetto A, Burrini AG, Collodel G, Ceccarini EC, Crisà N, Di Caro A, Estenoz M, Garbuglia AR, Massacesi A, et al. J Cell Biol. 1994 Nov;127(4):903-14. PMID: 7962075
6. Discovery and analysis of the first endogenous lentivirus. Aris Katzourakis, Michael Tristem, Oliver G. Pybus, and Robert J. Gifford Proc Natl Acad Sci U S A. 2007 April 10; 104(15): 6261–6265. PMCID: PMC1851024
7. Parallel Germline Infiltration of a Lentivirus in Two Malagasy Lemurs. Gilbert C, Maxfield DG, Goodman SM, Feschotte C, 2009 PLoS Genet 5(3): e1000425. doi:10.1371/journal.pgen.1000425
8. HIV-2 infection in 12 European residents : virus characteristics and disease progression. Van Der Ende M. E.; Schutten M.; Thaoi Duong LY; Gruters R. A.; Osterhaus A. D. M. E. AIDS ISSN 0269-9370 1996, vol. 10, no14, pp. 1649-1655 (23 ref.)
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