Where the Wild Things Are: Pathogenesis of SIV Infection in African Nonhuman Primate Hosts

African nonhuman primates that are natural hosts of simian immunodeficiency virus (SIV) are generally spared from disease progression. Pathogenic and nonpathogenic SIV infections share some major features: high viral replication, massive acute depletion of mucosal CD4(+) T cells, and partial control of the virus by both adaptive and innate immune responses. A key distinction of natural SIV infections is rapid and active control of immune activation and apoptosis of T cells that contributes to the integrity of mucosal barrier and lack of microbial translocation. This allows partial recovery of CD4(+) T cells and preservation of the function of other immune cell subsets. A better understanding of the mechanisms underlying the lack of disease in natural hosts for SIV infection will likely provide important clues as to the therapy of HIV-1 infection.