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"Heightened immune activation is the only clear cut difference between pathogenic and non-pathogenic infections with the immunodeficiency viruses," Kirchhoff added. "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."

Study coauthor Beatrice Hahn of the University of Alabama has previously shown that the two forms of HIV that infect humans originated from related SIVs found in different species of African primates. HIV-1--most closely related to an SIV strain found in chimpanzees--is the more virulent of the two human strains and the source of the majority of HIV infections throughout the world. The less pathogenic HIV-2 evolved from a virus that infects long-tailed relatives of baboons called sooty mangabeys. While HIV and SIV strains all infect T cells that are critical for a functional immune response, SIV usually does so without causing serious damage in their natural primate hosts.

Of more than 30 SIVs that have been molecularly characterized, all encode a Nef gene. However, Kirchhoff noted, functional information about the gene's role had been almost exclusively derived from the HIV-1 version of Nef. To get a broader evolutionary perspective in the current study, Kirchhoff's group examined nef gene variants taken from a variety of divergent SIV lineages.

Nef variants from the great majority of primate SIVs, including the less virulent human strain HIV-2, suppress the expression of a receptor normally found on the surface of T cells, making the immune cells less responsive to activation, the researchers found. In contrast, they report, the nef gene of HIV-1 and a subset of closely related SIVs failed to limit T cell activation and death.

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Source:Cell Press