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

Autor: Weymar, Georg H.J., Bar-On, Yotam, Oliveira, Thiago Y., Gaebler, Christian, Ramos, Victor, Hartweger, Harald, Breton, Gaëlle, Caskey, Marina, Cohn, Lillian B., Jankovic, Mila, Nussenzweig, Michel C.
Zdroj: Cell Reports; September 2022, Vol. 40 Issue: 10
Abstrakt: 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.
Databáze: Supplemental Index