International team finds gene variants that affect response to HIV...( ill the infected cell thereby stemming...)

The research team found that an individual's response to HIV infection depends heavily on the varieties -- or alleles -- of the genes encoding HLA molecules that the person has. But not all categories of HLA genes are equally important. The class I HLA alleles are divided into three categories -- HLA-A, HLA-B, and HLA-C. Specific HLA-B alleles generate much stronger immune responses than do other HLA alleles. For example, in a study of 706 infected individuals in South Africa who had not yet begun treatment, the type of HLA-B alleles a person had affected the amount of virus in the blood; the number of CD4 cells a person had (a common measure of immune system health); and immune reaction to proteins made by HIV. By contrast, different alleles of HLA-A and HLA-C genes had no effect on the immune response.

"The B alleles are doing most of the work," said Walker. Vaccine developers therefore should give close attention to responses generated by the HLA-B alleles, "since those seem to be the critical ones that influence viral load."

The involvement of the HLA-B alleles was particularly interesting to the researchers, since HLA-B alleles are much more diverse than either HLA-A or HLA-C alleles in human populations. Immunologists often have speculated that the greater diversity of HLA-B alleles indicates that they have been important during human history in fending off attacks from other pathogens. For instance, evolutionary forces may have promoted the diversification of HLA-B alleles so that human populations would present a multifaceted defense against infection.

In their Nature paper, Walker and his colleagues point out that the evolutionary influence of the HIV epidemic on HLA-B alleles already can be seen in the offspring of mothers infected with HIV. Mothers with protective alleles pass on HIV infection to their children less often than do mothers with alleles that do
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
8-Dec-2004