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Resistance to HIV-1 may be in the genes.

Scientists have suspected for several decades that an individual's genetic makeup may influence the body's response to various infectious diseases and have known that a percentage of those who are at high risk for acquiring HIV-1 resist the infection. Moreover, some persons infected with HIV-1 live for many years with no immune damage. Does this mean that a person's genetic makeup will prevent invasion by the HIV virus? Can a particular set of genes delay the progression of the disease to AIDS in those already infected?

Research groups around the country have been working feverishly to answer these questions. In one study, scientists at The University of Texas Health Science Center at San Antonio examined mutations in genes for immune molecules called chemokines and chemokine receptors in 1,090 individuals infected with HIV-1. In this group of patients, the researchers found a mutation in a chemokine receptor gene associated with a delay in HIV-1 disease progression in African-Americans and possibly also Hispanics and Native Americans, but not in Caucasians, as well as another mutation associated with an acceleration in the course of the disease.

HIV invades certain immune cells by taking advantage of molecules on the surface of those cells. One group of molecules used by HIV to enter the cell is called chemokine receptors. "Think of these molecules as keys that HIV uses to enter the cell," explains Sunil Ahuja, assistant professor of medicine and microbiology. "The recent discovery that HIV uses co-receptors [chemokine receptors] to enter the cell is a major breakthrough in HIV research. The first co-receptor that HIV latches onto to enter the cell is called CC chemokine receptor 5 [CCR5]. The HIV virus uses different co-receptors during different phases of the disease. Like a young man who chooses a partner at a dance, but quickly loses interest and selacts another partner, the HIV virus initially `dates' CCR5, but very quickly begins to mutate and loses its affinity for this co-receptor. It then attaches itself to other co-receptors, such as CC chemokine receptor 2 (CCR2), to enter other immune cells of the body, such as T cells."

Individuals who have a genetic mutation that completely prevents an expression of CCR5 resist acquiring HIV. "This mutation is very much like a gene condom. However, I should stress that this doesn't mean that one shouldn't use precautions, since some individuals who have this defect can still get infected. What is interesting, though, is this mutation is found in mostly Caucasians and not in minority groups, such as Hispanics and African-Americans." Almost one percent of healthy Caucasians in the U.S. have the mutation in both copies of CCR5 without any obvious immune defects.

A mutation in a different gene for a chemokine called SDF actually accelerates the progression of HIV toward AIDS. Individuals who have this particular mutation die about three years more quickly on average than those who lack the mutation.
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Publication:USA Today (Magazine)
Article Type:Brief Article
Date:Oct 1, 1998
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