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

  1. Author:
    Lian, Xiaodong
    Seiger, Kyra W
    Parsons, Elizabeth M
    Gao, Ce
    Sun, Weiwei
    Gladkov, Gregory T
    Roseto, Isabelle C
    Einkauf, Kevin B
    Osborn, Matthew R
    Chevalier, Joshua M
    Jiang, Chenyang
    Blackmer, Jane
    Carrington,Mary
    Rosenberg, Eric S
    Lederman, Michael M
    McMahon, Deborah K
    Bosch, Ronald J
    Jacobson, Jeffrey M
    Gandhi, Rajesh T
    Peluso, Michael J
    Chun, Tae-Wook
    Deeks, Steven G
    Yu, Xu G
    Lichterfeld, Mathias

  2. Author Address

    Infectious Disease Division, Brigham and Women 39;s Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., 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., Infectious Disease Division, Massachusetts General Hospital, Boston, MA 02114, USA., Case Western Reserve University, Cleveland, OH 44106, USA., University of Pittsburgh, Pittsburgh, PA 15260, USA., Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA., Division of HIV, Infectious Diseases and Global Medicine, University of California San Francisco, San Francisco, CA 94143, USA., Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA., Infectious Disease Division, Brigham and Women 39;s Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA. Electronic address: mlichterfeld@partners.org.,
    1. Year: 2022
    2. Date: Dec 28
    3. Epub Date: 2022 12 28
  2. Journal: Cell Host & Microbe
    1. 31
  4. Type of Article: Article
  1. Abstract:

    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. Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

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External Sources

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  2. DOI: 10.1016/j.chom.2022.12.002
  3. PMID: 36596305
  4. PII : S1931-3128(22)00574-1

Library Notes

  1. Fiscal Year: FY2022-2023
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