A dominant role for CD8+-T-lymphocyte selection in simian immunodeficiency virus sequence variation

J Virol. 2004 Dec;78(24):14012-22. doi: 10.1128/JVI.78.24.14012-14022.2004.

Abstract

CD8(+) T lymphocytes (CD8-TL) select viral escape variants in both human immunodeficiency virus and simian immunodeficiency virus (SIV) infections. The frequency of CD8-TL viral escape as well as the contribution of escape to overall virus diversification has not been assessed. We quantified CD8-TL selection in SIV infections by sequencing viral genomes from 35 SIVmac239-infected animals at the time of euthanasia. Here we show that positive selection for sequences encoding 46 known CD8-TL epitopes is comparable to the positive selection observed for the variable loops of env. We also found that >60% of viral variation outside of the viral envelope occurs within recognized CD8-TL epitopes. Therefore, we conclude that CD8-TL selection is the dominant cause of SIV diversification outside of the envelope.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Epitopes, T-Lymphocyte / genetics*
  • Epitopes, T-Lymphocyte / immunology
  • Genetic Variation*
  • Histocompatibility Antigens Class I / metabolism
  • Macaca mulatta
  • Molecular Sequence Data
  • Sequence Analysis, DNA
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / genetics*
  • Simian Immunodeficiency Virus / immunology
  • Viral Proteins / chemistry
  • Viral Proteins / genetics
  • Viral Proteins / metabolism

Substances

  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class I
  • Viral Proteins

Associated data

  • GENBANK/AY576480
  • GENBANK/AY576481
  • GENBANK/AY587015
  • GENBANK/AY588945
  • GENBANK/AY588946
  • GENBANK/AY597209
  • GENBANK/AY599198
  • GENBANK/AY599199
  • GENBANK/AY599200
  • GENBANK/AY599201
  • GENBANK/AY600249
  • GENBANK/AY603959
  • GENBANK/AY607701
  • GENBANK/AY607702
  • GENBANK/AY607703
  • GENBANK/AY607704
  • GENBANK/AY611486
  • GENBANK/AY611487
  • GENBANK/AY611488
  • GENBANK/AY611489
  • GENBANK/AY611490
  • GENBANK/AY611491
  • GENBANK/AY611492
  • GENBANK/AY611493
  • GENBANK/AY611494
  • GENBANK/AY611495