Emerging cytopathic and antigenic simian immunodeficiency virus variants influence AIDS progression

Genetic variants of human and simian immunodeficiency virus (HIV and SIV) t hat evolve during the course of infection and progression to AIDS are pheno typically and antigenically distinct from their progenitor viruses present at early stages of infection. However, it has been unclear how these late v ariants, which are typically T-cell tropic, cytopathic and resistant to neu tralizing antibodies, influence the development of clinical AIDS. To addres s this, we infected macaques with cloned SIVs representing prototype varian ts from early-, intermediate- and late-stage infection having biological ch aracteristics typical of viruses found at similar stages of HIV infection i n humans. These studies demonstrate that sequential, phenotypic and antigen ic variants represent viruses that have become increasingly fit for replica tion in the host, and our data support the hypothesis that emerging variant s have increased pathogenicity and drive disease progression in SIV and HIV infection.