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Single-cell Quantitation of mRNA and Surface Protein Expression in Simian Immunodeficiency Virus-infected CD4+ T Cells Isolated from Rhesus macaques
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Interactions between SIVNef, SIVGagPol and Alix correlate with viral replication and progression to AIDS in rhesus

Luciana Jesus da Costa1, Adriana Lopes Dos Santos, Robert Mandic

  • 1Departamento de Virologia, IMPPG, Universidade Federal do Rio de Janeiro, Brazil. ljcosta@micro.ufrj.br

Virology
|September 15, 2009
PubMed

Insights

Simian Immunodeficiency Virus (SIV) Nef protein interactions with GagPol and Alix are crucial for high viral loads and Simian AIDS (SAIDS) progression in rhesus macaques. Mutations preventing these interactions reduced disease severity in some animals.

Area of Science:

  • Virology
  • Immunology
  • Primate Models

Background:

  • Simian Immunodeficiency Virus (SIV) infection in rhesus macaques causes high viral loads and Simian AIDS (SAIDS).
  • The viral accessory protein Nef is essential for SIV pathogenesis in macaques and HIV pathogenesis in humans.
  • Previous research identified interactions between HIV Nef, HIV GagPol, and Alix as critical for optimal viral replication in cell culture.

Purpose of the Study:

  • To investigate the in vivo relevance of Nef-GagPol and Nef-Alix interactions in SIV pathogenesis.
  • To determine if these interactions correlate with viral load and disease progression to SAIDS in rhesus macaques.

Main Methods:

  • Infection of rhesus macaques with a mutant SIV(mac239) strain containing altered nef gene sequences essential for Nef-GagPol and Nef-Alix binding.
  • Monitoring viral replication, disease progression, and genetic/phenotypic reversion to wild-type SIV in infected macaques.

Main Results:

  • Two of four infected macaques showed robust viral replication and disease progression, ultimately dying of SAIDS.
  • These two macaques with severe disease reverted to wild-type SIV nef genotype and phenotype.
  • The other two macaques did not develop disease and maintained the mutant nef sequences, indicating reduced viral replication and pathogenesis.

Conclusions:

  • Interactions between Nef, GagPol, and Alix are critical for optimal SIV replication and progression to SAIDS in vivo.
  • Mutations disrupting these interactions can attenuate SIV pathogenesis in rhesus macaques.
  • These findings highlight the importance of Nef-mediated protein-protein interactions in viral disease progression.

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