Immunity in natural SIV infections

In stark contrast to human immunodeficiency virus (HIV)-infected individuals who, if left untreated, almost invariably progress to acquired immunodeficiency syndrome (AIDS), natural hosts for the simian immunodeficiency viruses (SIV) remain asymptomatic throughout the course of infection. This observation represents one of the main unresolved puzzles of AIDS research, particularly if one considers that natural SIV infections are characterized by chronically high levels of viraemia as well as intrinsic virus cytopathicity comparable with that of HIV. In this review, I discuss the basic immunological features of natural, nonpathogenic SIV infections, the evidence suggesting that attenuated, rather than extraordinarily strong, immune responses to the virus may favour their benign course, and the implications of these findings in terms of HIV therapy and vaccines.