Expanded cellular clones carrying replication-competent HIV-1 persist, wax, and wane

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  • Zheng Wang
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
  • Evelyn E. Gurule
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
  • Timothy P. Brennan
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
  • Jeffrey M. Gerold
    Program for Evolutionary Dynamics, Harvard University, Cambridge, MA 02138;
  • Kyungyoon J. Kwon
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
  • Nina N. Hosmane
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
  • Mithra R. Kumar
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
  • Subul A. Beg
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
  • Adam A. Capoferri
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
  • Stuart C. Ray
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
  • Ya-Chi Ho
    Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536;
  • Alison L. Hill
    Program for Evolutionary Dynamics, Harvard University, Cambridge, MA 02138;
  • Janet D. Siliciano
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
  • Robert F. Siliciano
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205;

Description

<jats:title>Significance</jats:title> <jats:p>The HIV-1 latent reservoir cannot be eradicated by antiretroviral therapy (ART). The reservoir is a major barrier to cure. To characterize the mechanisms that contribute to persistence of the latent reservoir, we examined clonally expanded cell populations carrying replication-competent HIV-1 and followed them longitudinally. Expanded clones harboring replication-competent HIV-1 were identified in all study participants, but these clones emerge and wane on a time scale of years. A similar pattern was identified in viruses sampled from residual viremia. The findings suggest that the latent reservoir is likely to be maintained through expansion driven by antigens and cytokines, and that the expansion is balanced with a constant cell loss.</jats:p>

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