This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In contrast to lentiviral infections of humans and macaques, SIV infection of natural hosts is non-pathogenic despite high levels of viral replication. However, the mechanisms underlying this absence of disease are unknown. Here we report that natural hosts for SIV infection express remarkably low levels of CCR5 on memory CD4+ T-cells isolated from blood, lymph nodes, and mucosal tissues. As this immunological feature is found in five different species of natural SIV hosts (sooty mangabeys, African green monkeys, mandrills, solatus, and chimpanzees) but absent in four non-natural/recent hosts (humans, rhesus, pigtail, cynomolgous macaques, and baboons), it may represent a key feature of the co-evolution between the virus and its natural hosts that led to a non-pathogenic infection. Beneficial effects of low CCR5 expression on CD4+ T-cells may include the reduction of target cells for viral replication and/or a decreased homing of activated CD4+ T-cells to mucosal tissues.
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