Contribution of CD8+ T cells to containment of viral replication and emergence of mutations in Mamu-A*01-restricted epitopes in Simian immunodeficiency virus-infected rhesus monkeys

J Virol. 2008 Jun;82(11):5631-5. doi: 10.1128/JVI.02749-07. Epub 2008 Mar 26.

Abstract

Here, we investigated the containment of virus replication in simian immunodeficiency virus (SIV) infection by CD8(+) lymphocytes. Escape mutations in Mamu-A*01 epitopes appeared first in SIV Tat TL8 and then in SIV Gag p11C. The appearance of escape mutations in SIV Gag p11C was coincident with compensatory changes outside of the epitope. Eliminating CD8(+) lymphocytes from rhesus monkeys during primary infection resulted in more rapid disease progression that was associated with preservation of canonical epitopes. These results confirm the importance of cytotoxic T cells in controlling viremia and the constraint on epitope sequences that require compensatory changes to go to fixation.

Publication types

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

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Epitopes, T-Lymphocyte / immunology*
  • Gene Products, gag / blood
  • Gene Products, tat / blood
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class I / metabolism
  • Macaca mulatta / immunology*
  • Macaca mulatta / virology
  • Mutation / genetics
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / physiology*
  • Virus Replication*

Substances

  • Epitopes, T-Lymphocyte
  • Gene Products, gag
  • Gene Products, tat
  • Histocompatibility Antigens Class I
  • Mamu-A 01 antigen