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

Cell reports | 2022

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.

Pubmed ID: 36070690 RIS Download

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: UM1 AI126620
  • Agency: NIAID NIH HHS, United States
    Id: UM1 AI100663
  • Agency: NCATS NIH HHS, United States
    Id: UL1 TR001866
  • Agency: NIAID NIH HHS, United States
    Id: P30 AI124414
  • Agency: NIAID NIH HHS, United States
    Id: U01 AI129825
  • Agency: NIAID NIH HHS, United States
    Id: UM1 AI164565
  • Agency: NIAID NIH HHS, United States
    Id: P01 AI100148
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI129795
  • Agency: NIAID NIH HHS, United States
    Id: UM1 AI126611

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