Progressive transformation of the HIV-1 reservoir cell profile over two decades of antiviral therapy.

Autor:	Lian X; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Seiger KW; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Parsons EM; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Gao C; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Sun W; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Gladkov GT; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Roseto IC; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Einkauf KB; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Osborn MR; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Chevalier JM; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Jiang C; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Blackmer J; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Carrington M; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA; Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA., Rosenberg ES; Infectious Disease Division, Massachusetts General Hospital, Boston, MA 02114, USA., Lederman MM; Case Western Reserve University, Cleveland, OH 44106, USA., McMahon DK; University of Pittsburgh, Pittsburgh, PA 15260, USA., Bosch RJ; Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA., Jacobson JM; Case Western Reserve University, Cleveland, OH 44106, USA., Gandhi RT; Infectious Disease Division, Massachusetts General Hospital, Boston, MA 02114, USA., Peluso MJ; Division of HIV, Infectious Diseases and Global Medicine, University of California San Francisco, San Francisco, CA 94143, USA., Chun TW; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA., Deeks SG; Division of HIV, Infectious Diseases and Global Medicine, University of California San Francisco, San Francisco, CA 94143, USA., Yu XG; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Lichterfeld M; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA. Electronic address: mlichterfeld@partners.org.
Jazyk:	angličtina
Zdroj:	Cell host & microbe [Cell Host Microbe] 2023 Jan 11; Vol. 31 (1), pp. 83-96.e5. Date of Electronic Publication: 2023 Jan 02.
DOI:	10.1016/j.chom.2022.12.002
Abstrakt:	HIV-1 establishes a life-long reservoir of virally infected cells which cannot be eliminated by antiretroviral therapy (ART). Here, we demonstrate a markedly altered viral reservoir profile of long-term ART-treated individuals, characterized by large clones of intact proviruses preferentially integrated in heterochromatin locations, most prominently in centromeric satellite/micro-satellite DNA. Longitudinal evaluations suggested that this specific reservoir configuration results from selection processes that promote the persistence of intact proviruses in repressive chromatin positions, while proviruses in permissive chromosomal locations are more likely to be eliminated. A bias toward chromosomal integration sites in heterochromatin locations was also observed for intact proviruses in study participants who maintained viral control after discontinuation of antiretroviral therapy. Together, these results raise the possibility that antiviral selection mechanisms during long-term ART may induce an HIV-1 reservoir structure with features of deep latency and, possibly, more limited abilities to drive rebound viremia upon treatment interruptions. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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