Virus Subtype-Specific Features of Natural Simian Immunodeficiency Virus SIV smm Infection in Sooty Mangabeys

Simian immunodeficiency virus (SIV) SIVsmm naturally infects sooty mangabeys (SMs) and is the source virus of pathogenic infections with human immunodeficiency virus type 2 (HIV-2) and SIVmac of humans and macaques, respectively. In previous studies we characterized SIVsmm diversity in naturally SIV-infected SMs and identified nine different phylogenetic subtypes whose genetic distances are similar to those reported for the different HIV-1 group M subtypes. Here we report that, within the colony of SMs housed at the Yerkes National Primate Research Center, at least four SIVsmm subtypes cocirculate, with the vast majority of animals infected with SIVsmm subtype 1, 2, or 3, resulting in the emergence of occasional recombinant forms. While SIVsmm -infected SMs show a typically nonpathogenic course of infection, we have observed that different SIVsmm subtypes are in fact associated with specific immunologic features. Notably, while subtypes 1, 2, and 3 are associated with a very benign course of infection and preservation of normal CD4+ T-cell counts, three out of four SMs infected with subtype 5 show a significant depletion of CD4+ T cells. The fact that virus replication in SMs infected with subtype 5 is similar to that in SMs infected with other SIVsmm subtypes suggests that the subtype 5-associated CD4+ T-cell depletion is unlikely to simply reflect higher levels of virus-mediated direct killing of CD4+ T-cells. Taken together, this systematic analysis of the subtype-specific features of SIVsmm infection in natural SM hosts identifies subtype-specific differences in the pathogenicity of SIVsmm infection.