• Jon is a contributing correspondent for Science.

HIV Impacts Human Genome

7 January 2005 (All day)

No vacancy. When CCL3L1 (red) occupies the CCR5 receptor on CD4 cells, it blocks HIV's entry.

Like a long-married couple, a virus and its host shape each other. HIV is no exception: a review of DNA from thousands of HIV-infected and uninfected people has found that the human genome may react to the invading virus. The genome stockpiles extra copies of immune genes that influence a person's HIV susceptibility as well as the course of disease. The findings could help improve studies of AIDS vaccines.

People typically have two copies of each gene (one from each parent), but stretches of DNA sometimes appear repeatedly. Many of the known duplications include immunity genes, inspiring the notion that these so-called segmental duplications protect against invaders. Sunil Ahuja, an infectious-disease specialist at the Veterans Administration Research Center for AIDS and HIV-1 Infection in San Antonio, Texas, wondered whether HIV might be the target of such an evolutionary response. The researchers focused on one human gene, CCL3L1. The gene codes for a signalling chemical called a chemokine, and it docks onto the same white blood cell receptor grabbed by HIV when the virus infects cells.

As part of their study, Ahuja and his colleagues examined a diverse cohort of 1000 HIV-infected people that the U.S. military has tracked for 20 years. After matching the cohort by race and ethnicity to more than 2000 uninfected controls, the researchers showed that duplications of CCL3L1 helped prevent infection and slow disease only if people had more copies than average for their racial or ethnic background. And those with fewer copies relative to members of their ethnic group--including babies of infected mothers--had increased susceptibility to HIV, they report in the 6 January Science Express. While the researchers can't be certain that these differences are due to virus-host evolution, the theory was bolstered by the finding that chimpanzees had more copies of the gene than Africans, who had more copies than more recently evolved Europeans.

Steven Wolinsky, a virologist at Northwestern University Medical School in Chicago, Illinois, whose lab also has studied the relationship between immune genes and HIV, calls the work "an intellectual and technical tour de force." Factoring in CCL3L1 status could lead to better-designed AIDS vaccine studies, says Ahuja. If a person has, say, a high level of genetic protection, a vaccine might appear to work when it didn't, or vice versa.

Related sites
Sunil Ahuja's site
Steven Wolinsky's site
Fact sheet on HIV transmission from the CDC

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