Posted on 01/24/2004 7:35:26 PM PST by Doc Savage
Personally, I don't buy the dissenters argument in total-- but I do think they make some good arguments (anti-viral drugs can be as or more toxic than just HIV, HIV in Africa is grossly overestimated for political reasons, etc.).
It's also clear that heterosexual AIDS is largely a myth. My uncle died of AIDS in 1991 after receiving HIV in a 1984 blood transplant. My aunt is alive and still healthy and HIV-free today. Though I really don't care to delve into my relatives sex life, the fact that so few wives of HIV-positive men get HIV suggests how hard it is to transmit vaginally. The stats I've heard are 1-1000 man-woman, and 1-8000 woman-man.
No, just the most incisive molecular knowledge on the pathophysiology. It is simple for you to do this if you are as familiar with the subject as you claim.
I am not interested in evangelism on the subject one way or the other and there is no need for you to get emotional.
Simply, how does the virus kill cells? Not how it binds to and enters and integrates in to the DNA and replicates.
What causes it to differ from every other retrovirus and kill cells to such an extent? How does HIV cause AIDS molecularly?
What's known on the subject?
For example, in this ecellent review article, Charting HIV's remarkable voyage through the cell: Basic science as a passport to future therapy , the authors describe the molecular biology of HIV very well. Much is know on this. But in their summary they write that, essentially, no one has any idea how or why it is killing cells -- not only the host cells but uninfected cells as well.
Besides creating a small animal model that recapitulates HIV pathogenic mechanisms, we need to better understand the mechanisms underlying viral cytopathicity. Such cell death is not only limited to infected targets but also involves uninfected bystander cells91. Proposed mechanisms for HIV killing of T cells include the formation of giant cell syncytia via interactions between gp120 with CD4 and chemokine receptors92, accumulation of unintegrated linear forms of viral DNA, proapoptotic effects of the Tat (ref. 93), Nef (ref. 94) and Vpr (ref. 95) proteins and the adverse effects conferred by the metabolic burden that HIV replication96 places on the infected cell. Notably, expression of Nef alone as a transgene in mice recapitulates many of the clinical features of AIDS including immunodeficiency and loss of CD4+ cells97.
I was hoping you could summarize the current theories for the viral cytopathicity. Maybe you still can.
What's hard to understand is why they continue their behavior in the face of overwhelming evidence that it is harmful to their health.
I agree. We agree.
I thus do not understand your next comment.
Inferred but never stated.
That is the problem. The AIDS industry wants us to believe this but they won't state it outright. Very strange for a business that puts major league athletes in Viagra ads. Why not a Magic Johnson ad for Protease Inhibitors? I think the reason is that Magic Johnson doesn't use Protease Inhibitors. If he does then we should know it for certain. Until then I am going to assume that it is just PR, a fat paycheck for Magic and nothing else. Endorsing a product is different that using that product. Just ask Magic.
I really think this thread deserves a Zot. It is nonsense. It is dangerous nonsense. If it is believed, people will die. It is worse than the dangerous nonsense spewed by a freeper last year about anti-aging.
I thought you were looking for some sort of exhaustive treatise on the virus and all molecular aspects of the dz, which I, as I said before, I will not take time to write out on this forum.
How exactly does HIV (itself - the virus) kill CD4 cells - it's not completely clear. However destruction of CD4 cells leads to a decrease in function of the imuune system as a whole as it is the CD4 cells that regulate the entire immune system through chemokines. It is other infectious diseases of malignancies that get you in AIDS, not the virus. However, a few of the mechanisms leading to CD4 dysfunction and depletion are (1) the accumulation of unintegreated viral DNA (2) RNAi (3)Intracellular gp120-CD4 autofusion events (4) loss of plamamembrane integrety through viral buddings (5) elimination of HIV infected cells through viral specific immune responses (6) abberant intracellular signaling (7) syncytium formation, and subsequent destruction by immune system (8) innocent bystander killing of viral antigen coated CD4 cells (9) direct viral-induction of apoptosis and (finally) (10) direct inhibition of lymphopoesis. All of thse will occur in a person infected with HIV, having an otherwise fine functioning immune system, and will lead to the dstruction of HIV ionfected cells CD4 or otherwise.
All this is in the before mentioned reading. I do know what I'm talking about, but the vast amount of knowledge and data in this area is just too exhaustive for me to give back to you on this forum, and if you want me to link to scientific articles, forget it, you can find the articles yourself. The primary ference I refered to earlier is as good as it gets on this subject.
Thanks.
The viral replicative cycle is well established, so that is not what I was looking for.
I'm interested in #10. Where and how does it directly inhibit lymphoeisis?
Also, most retroviruses have similar replicative cycles and analogous events to your 1 - 9 occur. Why is HIV cytopathic whereas others are not? Is this known?
Is it believed to be mainly CD4 related?
The articles I linked to and their refernces therein address it more. I thought you might have a good comprehensive review you knew of to reccommend.
Yep. I gave up trying to talk the Duesies out of their obsession years ago. It's a little like trying to talk geography with a flat-earther - they have a reasonable-sounding objection to every imaginable piece of evidence. Time wasted, IMHO.
Deusberg is one of the pioneers of retroviral research and his criticisms did not fall on deaf ears and were not consigned away as flat Earth stuff. In fact Science magazine published debates on the subject. Whereas they, I'm sure, felt he is wrong, he was still takn seriously enough to engender the public debate in Science and in other scientific journals. Hardly falt earth stuff. Maybe he is wrong, but not tin foil fringe or flat earth and you do yourself a disservice in trying to end debate in such a manner.
CD4 Tcells are responsible for secreting many different cytokines for regulating cell differentiation in the bone marrow, for instance IL-3, stimulates hematopoiesis, Il-5, stims growth and differentiation of eosinophils as well as B-cell growth, IL-7, stims pre-B and pre-T cell differentiation and production, and this is just a basic list. CD4 T cells CONTROL the immune system through chemical cytokines, and losing the CD4 cells leads to either (1) no immune response or (2) a completely inappropriate immune response, because the CD4 cells regulate the response of other immune cells.
Also, most retroviruses have similar replicative cycles and analogous events to your 1 - 9 occur. Why is HIV cytopathic whereas others are not? Is this known? Is it believed to be mainly CD4 related?
The reason for the "lag" from time of infection to time of aquired immune dz probably has to do with the fact that some cytokines have slightly overlapping functions, and the body, being cleverly made by God, is able to keep up a defense until such a time that the CD4 are sufficiently depleted that it matter not what other cyctokines other immune cells are producing, and yes, HIV is CD4 specific.
I did :-) The section in Harisson's is about as good and comprehensive as you're going to get.
AIDS really is a side-effect of destroying the cells that regulate and control the immune system as a whole. By analogy, without "mission control" it doesn't matter how good the astronauts and their equipment are, they're screwed.
AIDS could indeed be caused by a COMBINATION of HIV and use of poppers or other drugs
Drugs can obviously negatively effect any disease process, for instance certain steroids and anesthetics cause a decrease in immune function
AIDS could be an autoimmune reaction to HIV infection. This could account for the time difference between HIV infection and full blown AIDS -- it may take the body years to react.
The virus causes the immune system to destroy the very cells that regulate it so, yes, in this sense HIV causes AIDS through an indirect autoimmune reaction, which would be perfectly reasonable, excepting that the cells destroyed control the entire immune system.
AIDS could be the result of HIV infection plus some other viral agent.
AIDS is a "deficiency syndrome" caused secondarily to a viral infect, because the control cells are destroyed. So, AIDS is defined by the the "new" infection.
How come HIV infection does not flare up into AIDS? Considering the potency of the virus upon seroconversion, AIDS should quickly appear.
Not when one considers "cytokine overlap" in the immunological system. This would reuire the the controlling cells get to a low enough point that even the "overlap" is no longer helpful and we see the common menifestations of AIDS. Retroviruses can remain quite dormant, precipitating activation is required to get the "ball rolling"
All right. This is not direct, but indirect.
You also know that this is wrong. Completely myeolablated animals are able to be recuse and reonsititute their blood system by stem cell enriched bone marrow extracts. Cytokines are produced that regulated hematopoiesis in the marow stromal cells and also osteo cells.
CD4 cells are not necessary for hematopoiesis.
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