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Virology. 1995 Mar 10;207(2):528-42.

Progression to AIDS in macaques is associated with changes in the replication, tropism, and cytopathic properties of the simian immunodeficiency virus variant population.

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1
Department of Microbiology, University of Washington, Seattle 98195.

Abstract

Human immunodeficiency virus type 1 (HIV-1) typically evolves from a macrophage-tropic, noncytopathic virus at 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 virus phenotype may influence disease. Because simian immunodeficiency virus (SIV) infection in macaques is a common model system for HIV-1 pathogenesis, we determined whether SIV infection in macaques that develop simian AIDS is associated with a similar shift in viral tropism, replication, and cytopathic properties. The virus that infected the monkeys (SIVMneCL8) and predominated at early times in infection is a macrophage-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, exhibiting enhanced replication in CEM x 174 cells and an expanded host range that includes Molt-4 Clone 8 cells. Infections starting with equal doses of the viruses demonstrated that the late variants are cytopathic and syncytia-inducing compared to SIVMneCL8, but the variants replicate less efficiently in primary macaque macrophages. V3 sequences were generally conserved between the early and the late variants, suggesting that changes in SIVMne tropism, replication, and cytopathicity were apparently not due to alterations in V3. This study demonstrates important similarities in the phenotypic viral changes that accompany development of AIDS in SIV and HIV-1 infections and suggest that SIV may provide a model system for determining whether the rapidly replicating, T-cell-tropic cytopathic variants present late in infection and disease are indeed important in determining progression to AIDS.

PMID:
7886956
DOI:
10.1006/viro.1995.1113
[Indexed for MEDLINE]
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