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Genetic mutation
may have made HIV deadly

Genetic mutation
may have made HIV deadly

Mutations in a single gene may have turned the AIDS virus from a fairly benign infection of monkeys and apes into a global pandemic that has killed more than 25 million people in 25 years, researchers say. The virus in humans appears to have lost a genetic characteristic that protected the immune system in apes and monkeys, the researchers report in this week's issue of the journal Cell.

"The observed difference in Nef function may provide--for the first time--a mechanism to explain why many monkey species naturally infected with SIV do not develop disease," said Frank Kirchhoff of the University of Ulm in Germany, who helped lead the study.

Beatrice Hahn of the University of Alabama at Birmingham had earlier shown that the human immune deficiency virus, or HIV, descended from a chimpanzee virus called simian immunodeficiency virus, or SIV.

Many species of monkeys and chimps are infected with various strains of SIV, and it almost never causes disease. But HIV destroys the human immune system, leading to AIDS and usually death. There is no cure or vaccine.

Working with colleagues in Germany, Gabon, and elsewhere, Kirchhoff and Hahn's team focused on a protein and a gene called nef, found in all SIV and HIV strains. In SIV it helps ratchet down the activation of T-cells. These immune system cells are key to protection against disease, and HIV selectively infects T-cells known as CD4 helper T-cells.

In HIV infection, these T-cells destroy themselves in a process known as programmed cell death or apoptosis. But the SIV version of the virus seems to somehow shut off the death function.

"The findings suggest that the gene function was lost during viral evolution in a lineage that gave rise to HIV-1 and may have predisposed the simian precursor of HIV-1 for greater pathogenicity in humans," the researchers wrote.

This finding could open the door to new ways of treating HIV, they said.

"A strong immune response can be good in the short term, but if sustained for a long time as in those with HIV, it can exhaust the immune system," Kirchhoff said. "If you could somehow dampen the response, it might effectively convert the condition to the more chronic, asymptomatic infection seen in monkeys." (Reuters)

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