A single amino acid mutation in the envelope cytoplasmic tail restores the ability of an attenuated simian immunodeficiency virus mutant to deplete mucosal CD4+ T cells

J Virol. 2013 Dec;87(23):13048-52. doi: 10.1128/JVI.02126-13. Epub 2013 Sep 11.

Abstract

Disruption of the conserved motif GYxxØ in the simian immunodeficiency virus (SIV) SIVmac239 envelope (Env) cytoplasmic tail resulted in a virus (ΔGY) that exhibited a high plasma peak but uniquely failed to acutely deplete mucosal CD4(+) T cells. Here, we show that ΔGY containing a flanking S727P mutation that was acquired in ΔGY-infected macaques reacquired the ability to rapidly deplete CD4(+) T cells in lamina propria. This suggests that the GYxxØ motif and S727P each contribute to SIV's targeting to mucosal tissues.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Motifs
  • Animals
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • Gene Products, env / chemistry
  • Gene Products, env / genetics*
  • Gene Products, env / metabolism*
  • Macaca
  • Male
  • Mucous Membrane / immunology*
  • Mucous Membrane / virology
  • Mutation, Missense*
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / chemistry
  • Simian Immunodeficiency Virus / genetics*
  • Simian Immunodeficiency Virus / metabolism

Substances

  • Gene Products, env