Relationship between CD4 T cell turnover, cellular differentiation and HIV persistence during ART.

Autor: Bacchus-Souffan C; Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, California, United States of America., Fitch M; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California, United States of America., Symons J; The Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia., Abdel-Mohsen M; The Wistar Institute, Philadelphia, Pennsylvania, United States of America., Reeves DB; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America., Hoh R; Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital, University of California, San Francisco, California, United States of America., Stone M; Vitalant Research Institute and Department of Laboratory Medicine at the University of California, San Francisco, California, United States of America., Hiatt J; Medical Scientist Training Program & Biomedical Sciences Graduate Program, University of California, San Francisco, California, United States of America., Kim P; Infectious Diseases Section, Medical Service, San Francisco Veterans Affairs Medical Center, California, United States of America., Chopra A; Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Australia.; Center for Translational Immunology and Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America., Ahn H; Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, California, United States of America., York VA; Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, California, United States of America., Cameron DL; Division of Bioinformatics, Walter & Eliza Hall Institute of Medical Research, Parkville, Australia., Hecht FM; Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital, University of California, San Francisco, California, United States of America., Martin JN; Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital, University of California, San Francisco, California, United States of America., Yukl SA; Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital, University of California, San Francisco, California, United States of America.; Infectious Diseases Section, Medical Service, San Francisco Veterans Affairs Medical Center, California, United States of America., Mallal S; Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Australia.; Center for Translational Immunology and Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America., Cameron PU; The Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia., Deeks SG; Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital, University of California, San Francisco, California, United States of America., Schiffer JT; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America., Lewin SR; The Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia., Hellerstein MK; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California, United States of America., McCune JM; Global Health Innovative Technology Solutions/HIV Frontiers, Bill & Melinda Gates Foundation, Seattle, Washington, United States of America., Hunt PW; Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, California, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2021 Jan 19; Vol. 17 (1), pp. e1009214. Date of Electronic Publication: 2021 Jan 19 (Print Publication: 2021).
DOI: 10.1371/journal.ppat.1009214
Abstrakt: The precise role of CD4 T cell turnover in maintaining HIV persistence during antiretroviral therapy (ART) has not yet been well characterized. In resting CD4 T cell subpopulations from 24 HIV-infected ART-suppressed and 6 HIV-uninfected individuals, we directly measured cellular turnover by heavy water labeling, HIV reservoir size by integrated HIV-DNA (intDNA) and cell-associated HIV-RNA (caRNA), and HIV reservoir clonality by proviral integration site sequencing. Compared to HIV-negatives, ART-suppressed individuals had similar fractional replacement rates in all subpopulations, but lower absolute proliferation rates of all subpopulations other than effector memory (TEM) cells, and lower plasma IL-7 levels (p = 0.0004). Median CD4 T cell half-lives decreased with cell differentiation from naïve to TEM cells (3 years to 3 months, p<0.001). TEM had the fastest replacement rates, were most highly enriched for intDNA and caRNA, and contained the most clonal proviral expansion. Clonal proviruses detected in less mature subpopulations were more expanded in TEM, suggesting that they were maintained through cell differentiation. Earlier ART initiation was associated with lower levels of intDNA, caRNA and fractional replacement rates. In conclusion, circulating integrated HIV proviruses appear to be maintained both by slow turnover of immature CD4 subpopulations, and by clonal expansion as well as cell differentiation into effector cells with faster replacement rates.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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