Natural SIV Infection: Immunological Aspects

African non–human primates (NHPs) represent the only reservoir of simian immunodeficiency viruses (SIV) in the wild. Natural transmission of SIV in African NHPs is predominantly horizontal, and thought to occur through sexual contacts and/or bite wounds. Vertical transmission seems to be extremely rare. For three of the African NHPs – sooty mangabeys, African green monkeys and mandrills – it has been demonstrated that the SIV infection is generally non–pathogenic. We will refer to them as “natural hosts”. Natural hosts for SIV do not show any signs of AIDS despite chronically sustained high levels of viremia. In contrast to HIV-infected humans and SIV-infected macaques, natural hosts of SIV do not show evidence of chronic immune activation despite ongoing viral replication. The absence of chronic immune activation is likely the single most important factor contributing to the lack of disease progression in natural hosts. This observation has contributed to the increased attention given to the role of immune activation in HIV infection. Understanding the mechanisms by which natural hosts avoid immunopathology will most likely have major implications. The overall picture appears to be that natural hosts first mount a robust innate immune response, then there is an active dampening of inflammation. During the chronic phase, the lymph-node architecture and the mucosal integrity are maintained, and the immune functions are intact. Several hypotheses, which are not mutually exclusive, have been proposed to explain the regulation of immune activation in natural hosts. We will discuss in this chapter the characteristic features of the innate and adaptive immune responses in natural hosts infected by SIV as compared to those observed in pathogenic HIV and SIVmac infections, as well as the hypotheses suggested to explain the lack of chronic immune activation and maintenance of normal immune function in this model.