Simian immunodeficiency virus as a model of human HIV disease

Because of strong clinical, pathological, virological and immunological analogies with HIV infection of humans, infection of macaques with SIV provides a valuable model for exploring crucial issues related to both the pathogenesis and prevention of HIV infection. The model has offered a unique setting for the preclinical evaluation of drugs, vaccines and gene-therapies against HIV, and has helped to identify many virus and host determinants of lentiviral disease. For instance, the importance of an intact nef gene for efficient lentivirus replication and disease induction, and the protective ability of live attenuated, nef-deleted viruses have been first demonstrated in macaques using molecular clones of SIV. More recently, the development of chimeric HIV-SIV vectors able to establish infection and induce disease in macaques has provided new opportunities for the evaluation of vaccination strategies based upon HIV antigens. The aim of this review is to describe the natural course of SIV infection in macaques and to outline how this model has contributed to our understanding of the complex interaction between lentiviruses and host immune system.