PROGRESSION TO AIDS IN MACAQUES IS ASSOCIATED WITH CHANGES IN THE REPLICATION, TROPISM, AND CYTOPATHIC PROPERTIES OF THE SIMIAN IMMUNODEFICIENCY VIRUS VARIANT POPULATION

Human immunodeficiency virus type 1 (HIV-1) typically evolves from a m acrophage-tropic, noncytopathic virus al early asymptomatic stages of infection to a T-cell-tropic, cytopathic, and syncytia-inducing virus population as humans progress to AIDS. This suggests that changes in v irus phenotype may influence disease. Because simian immunodeficiency virus (SIV) infection in macaques is a common model system for HIV-1 p athogenesis, we determined whether SIV infection in macaques that deve lop simian AIDS is associated with a similar shift in viral tropism, r eplication, and cytopathic properties. The virus that infected the mon keys (SIVMneCL8) and predominated at early times in infection is a mac rophage-tropic virus that replicates with relatively low efficiency in human T cell lines. The variant populations that arise in macaques as they progress to AIDS are more infectious for human T cell lines, exh ibiting enhanced replication in CEMX174 cells and an expanded host ran ge that includes Molt-4 Clone 8 cells. Infections starting with equal doses of the viruses demonstrated that the late variants are cytopathi c and syncytia-inducing compared to SIVMneCL8, but the variants replic ate less efficiently in primary macaque macrophages. Vs sequences were generally conserved between the early and the late variants, suggesti ng that changes in SIVMne tropism, replication, and cytopathicity were apparently not due to alterations in V3. This study demonstrates impo rtant similarities in the phenotypic viral changes that accompany deve lopment of AIDS in SIV and HIV-1 infections and suggest that SIV may p rovide a model system for determining whether the rapidly replicating, T-cell-tropic cytopathic variants present late in infection and disea se are indeed important in determining progression to AIDS. (C) 1995 A cademic Press, Inc.