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HIV Targets the Masses

23 June 2003 (All day)
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Common denominator. HIV replicates most readily in people with immune system genes that are widespread.

Like an advertiser who targets mass markets, the AIDS-causing human immunodeficiency virus (HIV) more effectively attacks people who have common immune system genes than individuals with unusual variations. This new finding suggests that HIV is influencing how the human immune system evolves and that the human immune system puts evolutionary pressure on HIV as well. HIV's preference for common gene varieties might affect vaccine design.

The genes in question help certain immune cells package bits of viruses into so-called HLA class I proteins, which they affix to the outside surface of the cell. When a cytotoxic T cell runs into the exposed package, the T cell destroys the other cell--virus, package, and all. Mortality data have suggested that people with some types of HLA class I proteins are more likely than others to become infected with HIV and die. Each person carries two copies of each of three HLA class I genes; accounting for the more than 350 variants of the genes, this adds up to many thousands of possible combinations. Virologist Steven Wolinsky of Northwestern University in Chicago, Illinois, and colleagues wanted to determine whether they could find similarities between the HLA class I proteins that conferred resistance or susceptibility to HIV.

To do so, the team sequenced the DNA of the HLA class I genes of about 1000 HIV-infected men. Because some HLA class I proteins are shaped more alike than others, the proteins can be grouped into nine so-called supertypes. The researchers also determined how many T cells the patients had lost over 2 years or, in newly infected men, how much viral RNA they carried. No relationship turned up between T cell decline and supertype. However, the team found that men with the most common supertypes, called B7s and B27s, had the highest amount of viral RNA at the onset of infection. In contrast, men with the least common supertype, the B58 group, had the lowest amount. This result, published online this week in Nature Medicine, suggests that HIV has evolved to attack the most common supertype in a given population. "We're pushing on the microbes and they're pushing back on us," says Wolinsky.

The finding that HIV specializes suggests that HIV can sicken people more rapidly in homogenous populations, says immunologist Richard Koup of the National Institutes of Health Vaccine Research Center in Bethesda, Maryland. "The more diverse the population, the more difficult for the virus to escape" the immune system. The result reveals an obstacle for vaccine developers as well. Koup says some vaccines are being designed to help cytotoxic T cells control HIV infection, and that system depends on HLA class I proteins. But if HIV usurps the most common HLA variants, then stimulating cytotoxic T cells might not afford any protection at all. The research suggests, Koup says, that researchers will have to work around the cytotoxic T cell system.

Related site
Steven Wolinsky's home page

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