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

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.
Competing Interests: Declaration of interests Rockefeller University has patents on anti-HIV-1 antibodies 3BNC117 and 10-1074, on which M.C.N. is an inventor, that are licensed to Gilead.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)