Tat-specific Cytotoxic T Lymphocytes Select for SIV Escape Variants During Resolution of Primary Viraemia

Nature. 2000 Sep 21;407(6802):386-90. doi: 10.1038/35030124.

Abstract

Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections are characterized by early peaks of viraemia that decline as strong cellular immune responses develop. Although it has been shown that virus-specific CD8-positive cytotoxic T lymphocytes (CTLs) exert selective pressure during HIV and SIV infection, the data have been controversial. Here we show that Tat-specific CD8-positive T-lymphocyte responses select for new viral escape variants during the acute phase of infection. We sequenced the entire virus immediately after the acute phase, and found that amino-acid replacements accumulated primarily in Tat CTL epitopes. This implies that Tat-specific CTLs may be significantly involved in controlling wild-type virus replication, and suggests that responses against viral proteins that are expressed early during the viral life cycle might be attractive targets for HIV vaccine development.

Publication types

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

MeSH terms

  • AIDS Vaccines
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology
  • Gene Products, tat / chemistry
  • Gene Products, tat / genetics
  • Gene Products, tat / immunology*
  • Histocompatibility Antigens Class I / chemistry
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Macaca mulatta
  • Molecular Sequence Data
  • Mutation
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Viremia / immunology*

Substances

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