Gag-positive reservoir cells are susceptible to HIV-specific cytotoxic T lymphocyte mediated clearance in vitro and can be detected in vivo [corrected]

PLoS One. 2013 Aug 7;8(8):e71879. doi: 10.1371/journal.pone.0071879. eCollection 2013.

Abstract

Resting CD4+T cells infected with HIV persist in the presence of suppressive anti-viral therapy (ART) and are barriers to a cure. One potential curative approach, therapeutic vaccination, is fueled by recognition of the ability of a subset of elite controllers (EC) to control virus without therapy due to robust anti-HIV immune responses. Controllers have low levels of integrated HIV DNA and low levels of replication competent virus, suggesting a small reservoir. As our recent data indicates some reservoir cells can produce HIV proteins (termed GPR cells for Gag-positive reservoir cells), we hypothesized that a fraction of HIV-expressing resting CD4+T cells could be efficiently targeted and cleared in individuals who control HIV via anti-HIV cytotoxic T lymphocytes (CTL). To test this we examined if superinfected resting CD4+T cells from EC express HIV Gag without producing infectious virus and the susceptibility of these cells to CTL. We found that resting CD4+T cells expressed HIV Gag and were cleared by autologous CD8+T cells from EC. Importantly, we found the extent of CTL clearance in our in vitro assay correlates with in vivo reservoir size and that a population of Gag expressing resting CD4+T cells exists in vivo in patients well controlled on therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Cells, Cultured
  • Coculture Techniques
  • DNA, Viral / genetics
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HIV-1 / metabolism
  • Humans
  • Real-Time Polymerase Chain Reaction
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / virology
  • gag Gene Products, Human Immunodeficiency Virus / genetics
  • gag Gene Products, Human Immunodeficiency Virus / immunology*
  • gag Gene Products, Human Immunodeficiency Virus / metabolism

Substances

  • DNA, Viral
  • gag Gene Products, Human Immunodeficiency Virus