Distinct gene expression by expanded clones of quiescent memory CD4+ T cells harboring intact latent HIV-1 proviruses
Year: 2022
Type: article
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.
Source: Cell Reports
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,190
Funders: Howard Hughes Medical Institute, Bill and Melinda Gates Foundation, Gilead Sciences, Delaney AIDS Research Enterprise, City University of New York, Rockefeller University, National Institutes of Health, Center for AIDS Research, University of Washington, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences, Einstein-Rockefeller-CUNY Center for AIDS Research, Albert Einstein College of Medicine
Awards: G1153707119, G1648448198, BEAT-HIV: Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy, 3BNC117 and 10-1074 to suppress HIV-1 replication and reduce the reservoir, G3190470567, Fred Hutchinson Cancer Center - to discover circulating markers to determine the size of the HIV reservoir in the body, to clinically test interventions that might reduce the size..., Delaney AIDS Research Enterprise to Cure HIV, G5393093918, Optimization of Fc effector activity of anti-HIV antibodies to target HIV reservoir, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, G6919811502, ERC Einstein-Rockefeller-CUNY Center for AIDS research, REACH: Research Enterprise to Advance a Cure for HIV, Developing, Demonstrating, and Disseminating Innovative Programs to Achieve Translational Success
OpenAlex ID: W4294771189