HIV Achilles Heel

An international team of researchers has identified three gene variants that appear to have helped some HIV patients fight off the virus and delay the onset of full-blown AIDS.

The researchers expect the new findings to aid the search for an HIV vaccine that would work by boosting the protective effects of one or more of these genes and helping the body's own immune system overcome an infection.

The study, published in the journal Science, represents the first large collaborative project of the Center for HIV/AIDS Vaccine Immunology (CHAVI), a seven-year program directed by Barton Haynes, Frederic M. Hanes Professor of medicine at Duke. The results help researchers understand the variations in the way different patients respond to HIV infection, says David Goldstein, senior author of the paper and director of the Center for Population Genomics and Pharmacogenetics at Duke's Institute for Genome Sciences & Policy.

CHAVI researchers from several countries pooled their patient data. They used genome-wide screening technology to highlight gene variants, known as polymorphisms, in key immune-system cells that seemed especially effective at controlling the spread of HIV after infection.

Two of the polymorphisms were found in genes controlling the human leukocyte antigen (HLA) system, which plays a major role in the immune system by identifying foreign invaders and "tagging" them for destruction. Two HLA genes, known as HLA-A and HLA-B, are turned off by HIV when it enters the body, which keeps the immune system from recognizing the virus as foreign. But a third HLA gene, known as HLA-C, is not thought to be turned off by HIV-1.

The new results suggest that, for some individuals at least, HLA-C is involved in controlling HIV-1. Goldstein says the gene may represent an Achilles heel of HIV; if so, a vaccine could be designed to elicit an HLA-C response that HIV-1 might be unable to defuse.

These findings represent only the first of what investigators say will be a series of genome-wide studies to pinpoint additional targets for HIV vaccines. "As we expand the number of patients in future studies conducted by CHAVI researchers, we aim to discover even more polymorphisms that could provide additional clues of how some patients are better able to control the virus than others," Goldstein says. "This should ultimately lead to novel targets for vaccines, the primary goal of CHAVI."

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