Weak spot discovered in HIV virus

[johnny861]

http://www.sciencedaily.com/releases...0715165520.htm

Pathologists Believe They Have Pinpointed Achilles Heel Of HIV
ScienceDaily (July 16, 2008) — Human Immunodeficiency Virus (HIV) researchers at The University of Texas Medical School at Houston believe they have uncovered the Achilles heel in the armor of the virus that continues to kill millions.

The weak spot is hidden in the HIV envelope protein gp120. This protein is essential for HIV attachment to host cells, which initiate infection and eventually lead to Acquired Immunodeficiency Syndrome or AIDS. Normally the body’s immune defenses can ward off viruses by making proteins called antibodies that bind the virus. However, HIV is a constantly changing and mutating virus, and the antibodies produced after infection do not control disease progression to AIDS. For the same reason, no HIV preventative vaccine that stimulates production of protective antibodies is available.

The Achilles heel, a tiny stretch of amino acids numbered 421-433 on gp120, is now under study as a target for therapeutic intervention. Sudhir Paul, Ph.D., pathology professor in the UT Medical School, said, “Unlike the changeable regions of its envelope, HIV needs at least one region that must remain constant to attach to cells. If this region changes, HIV cannot infect cells. Equally important, HIV does not want this constant region to provoke the body’s defense system. So, HIV uses the same constant cellular attachment site to silence B lymphocytes - the antibody producing cells. The result is that the body is fooled into making abundant antibodies to the changeable regions of HIV but not to its cellular attachment site. Immunologists call such regions superantigens. HIV’s cleverness is unmatched. No other virus uses this trick to evade the body’s defenses.”

Paul is the senior author on a paper about this theory in a June issue of the journal Autoimmunity Reviews. Additional data supporting the theory are to be presented at the XVII International AIDS Conference Aug. 3-8 in Mexico City in two studies titled “Survivors of HIV infection produce potent, broadly neutralizing IgAs directed to the superantigenic region of the gp120 CD4 binding site” and “Prospective clinical utility and evolutionary implication of broadly neutralizing antibody fragments to HIV gp120 superantigenic epitope.”

First reported in the early 1980s, HIV has spread across the world, particularly in developing countries. In 2007, 33 million people were living with AIDS, according to a report by the World Health Organization and the United Nations.

Paul’s group has engineered antibodies with enzymatic activity, also known as abzymes, which can attack the Achilles heel of the virus in a precise way. “The abzymes recognize essentially all of the diverse HIV forms found across the world. This solves the problem of HIV changeability. The next step is to confirm our theory in human clinical trials," Paul said.

Unlike regular antibodies, abzymes degrade the virus permanently. A single abzyme molecule inactivates thousands of virus particles. Regular antibodies inactivate only one virus particle, and their anti-viral HIV effect is weaker.

“The work of Dr. Paul’s group is highly innovative. They have identified antibodies that, instead of passively binding to the target molecule, are able to fragment it and destroy its function. Their recent work indicates that naturally occurring catalytic antibodies, particularly those of the IgA subtype, may be useful in the treatment and prevention of HIV infection,” said Steven J. Norris, Ph.D., holder of the Robert Greer Professorship in the Biomedical Sciences and vice chair for research in the Department of Pathology and Laboratory Medicine at the UT Medical School at Houston.

The abzymes are derived from HIV negative people with the autoimmune disease lupus and a small number of HIV positive people who do not require treatment and do not get AIDS. Stephanie Planque, lead author and UT Medical School at Houston graduate student, said, “We discovered that disturbed immunological events in lupus patients can generate abzymes to the Achilles heel of HIV. The human genome has accumulated over millions of years of evolution a lot of viral fragments called endogenous retroviral sequences. These endogenous retroviral sequences are overproduced in people with lupus, and an immune response to such a sequence that resembles the Achilles heel can explain the production of abzymes in lupus. A small minority of HIV positive people also start producing the abzymes after decades of the infection. The immune system in some people can cope with HIV after all.”

Carl Hanson, Ph.D., who heads the Retrovirus Diagnostic Section of the Viral and Rickettsial Disease Laboratory of the California Department of Public Health, has shown that the abzymes neutralize infection of human blood cells by diverse strains of HIV from various parts of the world. Human blood cells are the only cells that HIV infects.

“This is an entirely new finding. It is a novel antibody that appears to be very effective in killing the HIV virus. The main question now is if this can be applied to developing vaccine and possibly used as a microbicide to prevent sexual transmission,” said David C. Montefiori, Ph.D., director of the Laboratory for AIDS Vaccine Research & Development at Duke University Medical Center. The abzymes are now under development for HIV immunotherapy by infusion into blood. They could also be used to guard against sexual HIV transmission as topical vaginal or rectal formulations.

“HIV is an international priority because we have no defense against it,” Paul said. “Left unchecked, it will likely evolve into even more virulent forms. We have learned a lot from this research about how to induce the production of the protective abzymes on demand. This is the Holy Grail of HIV research -- development of a preventative HIV vaccine.”

Major contributors to the research from the UT Medical School include Yasuhiro Nishiyama, Ph.D., and Hiroaki Taguchi, Ph.D., both with the Department of Pathology and Laboratory Medicine, and Miguel Escobar, M.D., of the Department of Pediatrics. Maria Salas and Hanson, both with the Viral and Rickettsial Disease Laboratory, contributed.

The research was funded by the National Institutes of Health and the Texas Higher Education Coordinating Board

[Roos]

That's awesome.

[matias]

I don't like the idea of using it as a topical vaginal or rectal formulation

why would anyone want any sort of excuse for infected people to fuck none-infected people

[clay donkey]

I give props to UT. That's smart thinking.

I will say that a lot of the time these guys come up with these big ideas that can never be done. They generate billions in research $ so everyone working on the project eats and sleeps well. Do we end up with a cure in the end? maybe if we are lucky.

I think AIDS has been a wake up call to society. I think AIDS has made people more aware of STDs in general. People are more carefull, and prevent not only AIDS but other stuff like herpies which doesn't kill and pregnancies. I think finding a cure for aids is great but I hope society doesn't just fucking without fucking thinking.

[Roos]

Originally Posted by matias

I don't like the idea of using it as a topical vaginal or rectal formulation

why would anyone want any sort of excuse for infected people to fuck none-infected people

I think it's awesome more in the fact that they could get closer to a cure.

[matias]

I do too .. I was just responding to the article itself

the article isn't specific about this and I am not sure if this would completely cure HIV or just easily keep HIV levels in someone that's infected to a very low number though

and even with a low hiv count and a low risk of infection, I don't think they should promote infected with non-infected intercourse

[xian]

there has been identified a popuation of Euros who are in effect immune to AIDs... just one more venue of research that mst be pursued to come this problem from multiple angles to arrive at a solution.

On a side note. One of the general tendencies if infectious diseases, especially fatal ones, is the gradual evolution toward less and less lethal forms. It is in the long term survival interests of the AIDS virus NOT to so weaken its host that death becomes inevitable. It is in its best interest to keep the host alive as long as possible so it can propagate more. Short acting very hot diseases with high mortality rates don't have the same opportunities to spread that slow acting less lethal viruses.

[SmackPickles]

and the day they find the cure...oh man...i can help but feel that we as people are way to irresponsible and selfish to deserve a cure. Cures should only be given out to the innocent and not the guy who buys hookers and cheats and so on.

[Roos]

Originally Posted by SmackPickles

Cures should only be given out to the innocent and not the guy who buys hookers and cheats and so on.

That's a fucking ignorant thing to say. My best friend is HIV positive and he never bought a hooker or cheated on anyone. Think before you type. People get HIV from numerous places and whether they are guilty or innocent of something, nobody deserves it. Moron.

[Damnsammit]

Money cures AIDS.

I'm not just sure... I'm HIV positive.

[xian]

Originally Posted by Roos

That's a fucking ignorant thing to say. My best friend is HIV positive and he never bought a hooker or cheated. Think before you type. People get HIV from numerous places and whether they are guilty or innocent of something, nobody deserves it. Moron.

Wow... how aggressive and mean of you

Of course no one deserves it but one can engage in behavior that makes it more or less likely to catch, yes?

I think what he's saying is that when solutions to bad/risky/dangerous behavior are discovered it makes it more likely that people will engage in that behavior not that everyone with AIDs caught it as a result of bad behavior.


Let me illustrate.... if we had a cure for an exploding liver due to cirrhosis fewer alcoholics would be encouraged to take better care of themselves and thus continue to engage in risky behavior that put others at risk as well.

[Left]

lol at the comments.

very inspiring and well written article. amazing research.
i hope it works in the human trials!

[MicahB]

another good step.

I'd assume getting a cure for HIV will help in a ton of other virus's as well.

Originally Posted by SmackPickles

Cures should only be given out to the innocent and not the guy who buys hookers and cheats and so on.

what's wrong w/ buying hookers?

[J. Fees]

http://www.thedailytube.com/video/85...e-cartoon-aids

[xian]

Originally Posted by MicahB

another good step.

I'd assume getting a cure for HIV will help in a ton of other virus's as well.

other auto-immunes.... lupus etc

Originally Posted by MicahB

what's wrong w/ buying hookers?

don't leave out the llello