The HIV-1 latent reservoir is largely sensitive to circulating T cells

Elife. 2020 Oct 6;9:e57246. doi: 10.7554/eLife.57246.

Abstract

HIV-1-specific CD8+ T cells are an important component of HIV-1 curative strategies. Viral variants in the HIV-1 reservoir may limit the capacity of T cells to detect and clear virus-infected cells. We investigated the patterns of T cell escape variants in the replication-competent reservoir of 25 persons living with HIV-1 (PLWH) durably suppressed on antiretroviral therapy (ART). We identified all reactive T cell epitopes in the HIV-1 proteome for each participant and sequenced HIV-1 outgrowth viruses from resting CD4+ T cells. All non-synonymous mutations in reactive T cell epitopes were tested for their effect on the size of the T cell response, with a≥50% loss defined as an escape mutation. The majority (68%) of T cell epitopes harbored no detectable escape mutations. These findings suggest that circulating T cells in PLWH on ART could contribute to control of rebound and could be targeted for boosting in curative strategies.

Keywords: CD8; HIV; T cell; hiv cure; hiv reservoir; human; immunology; inflammation.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Anti-HIV Agents / pharmacology*
  • CD4-Positive T-Lymphocytes / virology*
  • Cohort Studies
  • Epitopes / immunology
  • Female
  • HIV Infections / immunology*
  • HIV-1 / drug effects
  • HIV-1 / physiology
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Phylogeny
  • Viral Load / drug effects
  • Virus Latency / drug effects*
  • Virus Replication / drug effects

Substances

  • Anti-HIV Agents
  • Epitopes