Journal
VIROLOGY
Volume 394, Issue 1, Pages 47-56Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2009.08.024
Keywords
SIV; HIV; Nef; Monkey infection; Pathogenesis; Disease progression; GagPol; Alix
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Funding
- NIGMS NIH HHS [P50 GM082250, P50 GM082250-02] Funding Source: Medline
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Infection with Simian Immunodeficiency Virus (SIV) leads to high viral loads and progression to Simian AIDS (SAIDS) in rhesus macaques. The viral accessory protein Nef is required for this phenotype in monkeys as well as in HIV-infected humans. Previously, we determined that HIVNef binds HIVGagPol and Alix for optimal viral replication in cells. In this study, we demonstrated that these interactions could correlate with high viral loads leading to SAIDS in the infected host. By infecting rhesus macaques with a Mutant SIVmac239, where sequences in the nef gene that are required for these interactions were Mutated, we observed robust viral replication and disease in two Out Of four monkeys, where they reverted to the wild type genotype and phenotype. These two rhesus macaques also died of SAIDS. Two other monkeys did not progress to disease and continued to harbor mutant nef sequences. We conclude that interactions between Nef, GagPol and Alix contribute to optimal viral replication and progression to disease in the infected host. (C) 2009 Elsevier Inc. All rights reserved.
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