In recent years there has been a growing appreciation of the importance of “comparative AIDS research” (i.e., studies of HIV and SIV infections in different hosts) as a tool to understand HIV pathogenesis and to improve both prevention and therapy of HIV infection. In this presentation I will provide a state-of-the-art summary of the field of natural, nonprogressive SIV infections of hosts such as sooty mangabeys and African green monkeys.
Natural SIV infections are the result of an evolutionary adaptation that allows a peaceful coexistence of lentiviruses and the primate immune system. This adaptation does not involve control of viremia but, rather, is characterized by phenotypic changes to CD4+ T cells, limited immune activation and preserved mucosal immunity, all of which contribute to the benign phenotype of these infections and, possibly, to the reduced rates of vertical SIV transmission.
In this presentation, I will: (i) summarize the main immunological and virological features of natural, non-pathogenic SIV infections, including the ability to mount robust innate immune responses to the virus; (ii) revisit the main hypotheses that were proposed to explain the apathogenicity of these infections; and (iii) discuss how a different pattern of in vivo infected CD4+ T cells, with central memory cells being relatively spared from direct virus infection, may preserve CD4+ T cell homeostasis and reduce immune activation in SIV-infected natural hosts.