The impact of viral evolution and frequency of variant epitopes on primary and memory human immunodeficiency virus type 1-specific CD8⁺ T cell responses

Virology. 2014 Feb;450-451:34-48. doi: 10.1016/j.virol.2013.10.015. Epub 2013 Dec 20.

Abstract

It is unclear if HIV-1 variants lose the ability to prime naïve CD8(+) cytotoxic T lymphocytes (CTL) during progressive, untreated infection. We conducted a comprehensive longitudinal analysis of viral evolution and its impact on primary and memory CD8(+) T cell responses pre-seroconversion (SC), post-SC, and during combination antiretroviral therapy (cART). Memory T cell responses targeting autologous virus variants reached a nadir by 8 years post-SC with development of AIDS, followed by a transient enhancement of anti-HIV-1 CTL responses upon initiation of cART. We show broad and high magnitude primary T cell responses to late variants in pre-SC T cells, comparable to primary anti-HIV-1 responses induced in T cells from uninfected persons. Despite evolutionary changes, CD8(+) T cells could still be primed to HIV-1 variants. Hence, vaccination against late, mutated epitopes could be successful in enhancing primary reactivity of T cells for control of the residual reservoir of HIV-1 during cART.

Keywords: Autologous viral variants; HIV-1; Memory T cell responses; Primary T cell responses; cART.

Publication types

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

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • CD8-Positive T-Lymphocytes / immunology
  • Cohort Studies
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology*
  • Evolution, Molecular*
  • HIV Infections / drug therapy
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / genetics*
  • HIV-1 / immunology
  • HIV-1 / isolation & purification
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Male
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / virology
  • Viral Proteins / genetics
  • Viral Proteins / immunology

Substances

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