Comprehensive Analyses of a Unique HIV-1-infected Nonprogressor Reveal a Complex Association of Immunobiological Mechanisms in the Context of Replication-Incompetent Infection

Virology. 2002 Dec 20;304(2):246-64. doi: 10.1006/viro.2002.1706.

Abstract

We recently demonstrated that a unique HIV-1-infected nonprogressor was infected with a nonevolving replication-incompetent HIV-1 strain, showing a total absence of viral evolution in vivo. Potent immune responses against HIV-1 were observed in his PBMC, despite an apparent lack of viral replication for at least 8 years. His PBMC resisted superinfection with CCR5, CXCR4, and dual-tropic HIV-1 strains, although highly purified CD4+ T cells supported infection, but without any visible cytopathic effect. Potent noncytolytic CD8+ T cell antiviral activity was shown to protect his PBMC from productive infection. This activity was not mediated by several known chemokines or IFN-gamma, which were produced at high levels after PHA activation of his CD8+ T cells, indicating the action of other CAF-like CD8 factors. This antiviral activity was a memory response, induced by HIV-specific stimulation to similar levels observed by PHA stimulation, but absent in ex vivo resting T cells. Immunological mechanisms associated with this antiviral suppressive activity included vigorous Gag-specific helper T cell proliferative responses and high-level IFN-gamma release by both CD4 and CD8 T cells. These responses were broadly directed against multiple Gag epitopes, both previously reported and some novel epitopes. Strong HIV-specific helper T cell function was also associated with strong neutralizing antibodies. Understanding how to induce these protective immune responses in other individuals could provide a major step forward in the design of effective immunotherapies or vaccines against HIV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / immunology*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Chemokines / physiology
  • Cytokines / physiology
  • HIV Antibodies / immunology
  • HIV-1 / classification
  • HIV-1 / immunology*
  • HIV-1 / physiology
  • Humans
  • Immunophenotyping
  • Male
  • Middle Aged
  • Phylogeny
  • Receptors, CCR2
  • Receptors, CCR5 / genetics
  • Receptors, Chemokine / genetics
  • T-Lymphocytes, Cytotoxic / immunology
  • Virus Replication*

Substances

  • CCR2 protein, human
  • Chemokines
  • Cytokines
  • HIV Antibodies
  • Receptors, CCR2
  • Receptors, CCR5
  • Receptors, Chemokine