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3 April 2006
New HIV Research May Yield Better Treatments
by George Atkinson

While existing treatments for HIV/AIDS are reasonably effective, medical experts are worried by the emergence of new strains of drug resistant HIV and an apparent increase in risky sexual behaviors. Researchers in New York believe that the emergence of new HIV variants could be related to events like POZ Parties, where HIV infected men engage in unprotected sex. And recent research carried out in Florida has only amplified such concerns; indicating that up to one-third of men who have sex with men may be engaging in unprotected anal intercourse while on vacation. The emergence of drug resistant HIV super-infections could be closely tied to such behaviors, and while health authorities are looking to ramp-up prevention efforts, researchers are continuing to search for better treatments to tackle these new HIV strains.

One of the most promising new areas of research comes from Ohio State University, where researchers have discovered a previously unknown mechanism that the body's cells use to fight off the HIV virus. Researcher Richard Fishel explained that two proteins that normally help repair cellular DNA can also destroy the DNA made by HIV after it enters a human cell. Without this DNA, the HIV virus cannot survive and reproduce.

"Our findings identify a new potential drug target, one that involves a natural host defense, HIV treatments that target cellular components should be far less likely to develop resistance," said Fishel.

He explained that HIV carries its genetic material in the form of RNA (ribonucleic acid) and once inside a cell, the virus makes a copy of its genes in the form of DNA. This DNA copy - known as cDNA - then travels to the cell nucleus, where it becomes integrated into the cell's DNA. It then generates yet more HIV, which eventually leads to full-blown AIDS. For an infection to gain a foothold, HIV requires DNA repair enzymes provided by the host cell to finish the integration process.

But it seems that two of these repair enzymes - dubbed XPB and XPD - can actually destroy the HIV cDNA before it is integrated into the chromosome. "Overall, our results indicate that these two DNA repair proteins participate in the destruction of HIV cDNA in cells," Fishel said. "This process reduces the pool of HIV cDNA that can integrate into host chromosomes, thereby protecting cells from infection." With a view to developing new treatments, Fishel is now conducting ongoing experiments to learn exactly how the proteins destroy the HIV cDNA.

Meanwhile, at the University of Warwick in England, scientists have developed a new kind of molecule which they believe could ultimately lead to the development of a vaccine against HIV. Using genetically modified tobacco, the researchers say they have overcome a major barrier that has so far frustrated attempts to turn plants into economically viable "bioreactors" for vaccines.

Warwick's Patricia Obregon is working with HIV's p24 core protein, which plays a central role in eliciting the immune response to HIV infection. Obregon's team have found a way to significantly boost HIV-1p24 protein production in plants by producing an entirely new molecule - a fusion of the HIV-1p24 protein and part of another protein, human immunoglobulin A (IgA) - a major component of the immune system. The team found that the HIV-1p24 antigen produced in this way elicited an appropriate immune response in mice.

Pharmaceuticals derived from plants are of great interest to researchers because of their enormous potential for economy and scale of production. "Producing vaccines this way could make treatments accessible to poor populations in developing countries - which is where these medicines are needed the most," explained Obregon.

Based on material from Ohio State University, the University of Warwick and the New York Academy of Medicine

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