Paired quantitative and qualitative assessment of the replication-competent HIV-1 reservoir and comparison with integrated proviral DNA

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  • Julio C. C. Lorenzi
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065;
  • Yehuda Z. Cohen
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065;
  • Lillian B. Cohn
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065;
  • Edward F. Kreider
    Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
  • John P. Barton
    Department of Chemical Engineering, Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139;
  • Gerald H. Learn
    Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
  • Thiago Oliveira
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065;
  • Christy L. Lavine
    Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215;
  • Joshua A. Horwitz
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065;
  • Allison Settler
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065;
  • Mila Jankovic
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065;
  • Michael S. Seaman
    Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215;
  • Arup K. Chakraborty
    Department of Chemical Engineering, Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139;
  • Beatrice H. Hahn
    Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
  • Marina Caskey
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065;
  • Michel C. Nussenzweig
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065;

Description

<jats:title>Significance</jats:title> <jats:p> A reservoir of latently infected cells poses the greatest challenge to HIV-1 eradication. Efforts to develop strategies to eliminate the reservoir have been hampered, in part, by the lack of a precise understanding of the cellular and molecular nature of this reservoir. We describe a new method to analyze the replication-competent latent reservoir quantitatively and qualitatively. We find that over 50% of the replication-competent viruses in the reservoir form part of groups with identical <jats:italic>env</jats:italic> sequences. However, a negative correlation exists between integrated proviral clones and replication-competent viruses, such that the larger the proviral clone, the lower is its probability of representing a replication-competent virus. </jats:p>

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