Tertiary mutations stabilize CD8+ T lymphocyte escape-associated compensatory mutations following transmission of simian immunodeficiency virus

J Virol. 2014 Mar;88(6):3598-604. doi: 10.1128/JVI.03304-13. Epub 2013 Dec 26.

Abstract

Compensatory mutations offset fitness defects resulting from CD8(+) T lymphocyte (CD8(TL))-mediated escape, but their impact on viral evolution following transmission to naive hosts remains unclear. Here, we investigated the reversion kinetics of Gag(181-189)CM9 CD8(TL) escape-associated compensatory mutations in simian immunodeficiency virus (SIV)-infected macaques. Preexisting compensatory mutations did not result in acute-phase escape of the SIVmac239 CD8(TL) epitope Gag(181-189)CM9 and instead required a tertiary mutation for stabilization in the absence of Gag(181-189)CM9 escape mutations. Therefore, transmitted compensatory mutations do not necessarily predict rapid CD8(TL) escape.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology
  • Gene Products, gag / genetics*
  • Gene Products, gag / immunology*
  • Macaca mulatta
  • Molecular Sequence Data
  • Mutation*
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / transmission
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / immunology*

Substances

  • Epitopes, T-Lymphocyte
  • Gene Products, gag