HIV entry to host cells begins with binding of the viral envelope protein to CD4 molecules on the host cell surface. This binding initiates conformational changes in the envelope protein that result in binding to a coreceptor (CCR5 or CXCR4), exposure of a previously hidden domain in the viral protein, insertion of a viral fusion peptide into the host-cell membrane and fusing the viral and cell membranes. Each of these steps provides an opportunity for intervention to prevent viral entry, and a number of agents targeting these steps are in development. Studies of coreceptor inhibitors and fusion inhibitors have indicated the presence of host and viral factors that can result in variability of antiretroviral effect. Improved understanding of these factors will help to guide clinical use of these new agents. This article summarizes a presentation by Robert W. Doms, MD, PhD, at the International AIDS Society-USA course in Chicago in May 2004.
The fact that some healthy individuals, who were repeatedly exposed to HIV infection but remained uninfected, were found to be homozygous for a 32-bp deletion in the CCR5 gene (20, 42, 52) triggered the search for CCR5 antagonists as potential anti-HIV agents.
CCL3L1, the gene identified in the new study, makes a protein that also binds to CCR5. Ahuja suggests that people with extra copies of this gene are more resistant to HIV because they make more CCL3L1, and cuts the amount of CCR5 around for the virus to attach to and therefore prevents it from entering white blood cells.
It's an interesting press release and thread. Here's the title of the original article and abstract, i.e. a brief summary.
Immunoglobulins (Igs) in uninfected humans recognize residues 421-433 located in the B cell superantigenic site (SAg) of the HIV envelope protein gp120 and catalyze its hydrolysis by a serine protease-like mechanism. The catalytic activity is encoded by germline Ig variable (V) region genes, and is expressed at robust levels by IgMs and IgAs but poorly by IgGs. Mucosal IgAs are highly catalytic and neutralize HIV, suggesting that they constitute a first line of defense against HIV. Lupus patients produce the Igs at enhanced levels. Homology of the 421-433 region with an endogenous retroviral sequence and a bacterial protein may provide clues about the antigen driving anti-SAg synthesis in lupus patients and uninfected subjects. The potency and breadth of HIV neutralization revives hopes of clinical application of catalytic anti-421-433 Igs as immunotherapeutic and topical microbicide reagents. Adaptive improvement of anti-SAg catalytic Igs in HIV infected subjects is not customary. Further study of the properties of the naturally occurring anti-SAg catalytic Igs should provide valuable guidance in designing a prophylactic vaccine that amplifies protective catalytic immunity to HIV.
Here are the questions if HIV does not cause AIDS:
How did large numbers of people in China get it after they donated blood? 23 August 2001
The Agence France Presse (AFP) reported that China admitted for the first time that tens of thousands of its citizens have been infected with the AIDS virus. Deputy Health Minister Yin Dakui stated, A large number of blood sellers have been infected with HIV due to illegal blood plasma. The illegal blood collection stations usually collected and pooled blood from poor farmers, separated the plasma, and then returns the contaminated blood back to the donators. Yin said, that "so far the problem of HIV infection caused by blood donations had only affected several provinces in central China.
How do you explain the drop in new HIV/AIDS cases after blood was screened for HIV before transfusion of blood and blood products?
Why does giving antiretroviral drugs to HIV positive pregnant women just before and around the birth of their children reduce the rate of HIV positive children being born?
Why do HIV negative children breastfeeding from HIV positive mothers get AIDS and die from it?
Why do the highly active antiretroviral therapy(HAART) drugs decrease mortality and increase longevity?
As far as I'm concerned, Peter Duesberg has only one valid question - the diagnostic accuracy in Africa, but he ignores all of the good outcomes from using antiretroviral drugs there. He's fixated on homosexuals using amyl nitrate "poppers." Other than being a mind altering substance and less inhibited about being promiscuous, I don't see an explanation from Duesberg for why homosexuals get AIDS.
The same goes for intravenous drug abusers. They don't get AIDS if they use clean needles and don't share.(PERIOD!) And yes, they do exist. Not everyone is your typical junkie. Chronic alcoholics are more readily recognized for being immunocompromised. Check the abstract with this link. I almost forgot it.
P.S. If the CDC is such an all powerful entity, then why aren't HIV positive people who have spread it to more than one person quarantined?
Now that is the best question raised so far!!!
OK, after spending many hours reading both sides of this debate I think it's safe to say that HIV plays a very major role in AIDS, although we do not full understand how it does it.
==Unwelcome guests with master keys: how HIV enters cells and how it can be stopped.
If HIV is not the cause of AIDS, then they might as well be talking about how any number of harmless retroviruses bind to their host.
==Inhibition of Human Immunodeficiency Virus Replication by a Dual CCR5/CXCR4 Antagonist
Again, if HIV is not the cause of AIDS, this information is worthless.
==Gene fights off HIV
==Pathologists Believe They Have Pinpointed Achilles Heel Of HIV
==Catalytic antibodies to HIV: Physiological role and potential clinical utility.
More on your remaining questions later.
Perhaps this will help you understand (note the other drugs listed):
Evidence continued to mount strongly supporting a connection between nitrite use, other recreational drugs, and AIDS. This included articles by James Goedert and William Blattner from the NIH, the CDC's sister institution (Goedert et al., 1982), by Harry Haverkos with the CDC's Kaposi's Sarcoma Opportunistic Infection (KSOI) task force, and an abundance of other studies on the immunotoxic and carcinogenic effects of nitrite inhalants (Newell et al., 1984; Haverkos & Dougherty, 1988a; Haverkos & Dougherty, 1988b). An English team reported in 1984 that 86% of male homosexual AIDS patients from St Mary's Hospital in London had inhaled nitrites compared to 86.4% from clinics in New York, San Francisco, and Atlanta (McManus et al., 1982). In 1983, two dozen of America's leading AIDS investigators including Friedman-Kien, Curran, and CDC worker Harold Jaffe, later director of the CDC's HIV/AIDS Division, had conducted extensive epidemiological studies which revealed overwhelming drug use, including nitrite inhalants, cocaine, and amphetamines by all homosexual AIDS patients studied (Table 2) (Jaffe et al., 1983).
Drugs seemed to be the most plausible explanation for the restriction of AIDS to risk groups, because drug consumption was the only health risk male homosexuals and intravenous drug users had in common (Krieger & Caceres, 1985). This original drug-AIDS hypothesis was euphemistically called the 'lifestyle hypothesis' (Oppenheimer, 1992). Indeed, massive supplies of illicit recreational drugs such as nitrite (poppers) and ethylchloride inhalants, cocaine, heroin, amphetamines, phenylcyclidine, and LSD had reached America and Europe since the Vietnam War and were the only statistically significant new health risks that had affected these countries since World War II (see page 103).
Suddenly, after the announcement of the discovery of the 'AIDS virus' by Gallo at the international press conference in Washington on April 23, 1984 (see above), the lifestyle hypothesis was dropped without notice - as if it never existed - in favor of the virus-AIDS hypothesis. Since then, any revisionism was immediately regarded as obsolete, or in the words of David Baltimore even as a 'pernicious and irresponsible' obstacle (Booth, 1988) in the war against the AIDS virus (Weiss & Jaffe, 1990; Cohen, 1994a; Duesberg, 1996d; O'Brien & Goedert, 1996; O'Brien, 1997). Henceforth, recreational drugs were only studied, if at all, as risk factors of HIV infection or as obstacles in anti-HIV medications.
Actually, the number of AIDS cases continued its steep rise long after blood products began to be screened for HIV: