Lessons learned from the natural hosts of HIV-related viruses.

The fact that human immunodeficiency virus (HIV) causes a deadly disease in humans whereas its simian counterparts, the simian immunodeficiency viruses (SIVs), are virtually nonpathogenic in their natural hosts remains a fundamental mystery of modern medicine. Arguably, the pathogenesis of HIV infection will remain poorly understood until the mechanisms responsible for the AIDS resistance of natural SIV hosts are fully explained. Over the past few years, some key features of natural SIV infections have been described in studies conducted predominantly in sooty mangabeys (SMs), African green monkeys (AGMs), and mandrills. Natural SIV hosts are able to avoid the chronic, generalized immune system activation that is associated with disease progression in HIV-infected individuals and have evolved to down-modulate the expression of CCR5 on CD4(+) T cells. Better elucidation of the mechanisms underlying the lack of disease progression of natural SIV infections holds promise for the design of novel preventive and therapeutic approaches to HIV infection.