Interactions between SIVNef, SIVGagPol and Alix correlate with viral replication and progression to AIDS in rhesus macaques

Luciana Jesus da Costa, Adriana Lopes dos Santos, Robert Mandic, Karen Shaw, Renato Santana de Aguiar, Amilcar Tanuri, Paul A Luciw, B. Matija Peterlin

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)47-56
Number of pages10
JournalVirology
Volume394
Issue number1
DOIs
StatePublished - Nov 10 2009

Keywords

  • Alix
  • Disease progression
  • GagPol
  • HIV
  • Monkey infection
  • Nef
  • Pathogenesis
  • SIV

ASJC Scopus subject areas

  • Virology

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    Jesus da Costa, L., Lopes dos Santos, A., Mandic, R., Shaw, K., Santana de Aguiar, R., Tanuri, A., Luciw, P. A., & Peterlin, B. M. (2009). Interactions between SIVNef, SIVGagPol and Alix correlate with viral replication and progression to AIDS in rhesus macaques. Virology, 394(1), 47-56. https://doi.org/10.1016/j.virol.2009.08.024