Distinct gene expression by expanded clones of quiescent memory CD4+ T cells harboring intact latent HIV-1 proviruses

Cell Rep. 2022 Sep 6;40(10):111311. doi: 10.1016/j.celrep.2022.111311.

Abstract

Antiretroviral therapy controls, but does not cure, HIV-1 infection due to a reservoir of rare CD4+ T cells harboring latent proviruses. Little is known about the transcriptional program of latent cells. Here, we report a strategy to enrich clones of latent cells carrying intact, replication-competent HIV-1 proviruses from blood based on their expression of unique T cell receptors. Latent cell enrichment enabled single-cell transcriptomic analysis of 1,050 CD4+ T cells belonging to expanded clones harboring intact HIV-1 proviruses from 6 different individuals. The analysis reveals that most of these cells are T effector memory cells that are enriched for expression of HLA-DR, HLA-DP, CD74, CCL5, granzymes A and K, cystatin F, LYAR, and DUSP2. We conclude that expanded clones of latent cells carrying intact HIV-1 proviruses persist preferentially in a distinct CD4+ T cell population, opening possibilities for eradication.

Keywords: CP: Immunology.

Publication types

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

MeSH terms

  • CD4-Positive T-Lymphocytes / metabolism
  • Clone Cells
  • DNA-Binding Proteins / metabolism
  • Gene Expression
  • HIV Infections*
  • HIV Seropositivity*
  • HIV-1* / genetics
  • HIV-1* / metabolism
  • Humans
  • Nuclear Proteins / metabolism
  • Proviruses / genetics
  • Proviruses / metabolism
  • Virus Latency / genetics

Substances

  • DNA-Binding Proteins
  • LYAR protein, human
  • Nuclear Proteins