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Distinct viral reservoirs in individuals with spontaneous control of HIV-1

  1. Author:
    Jiang, Chenyang [ORCID]
    Lian, Xiaodong [ORCID]
    Gao, Ce [ORCID]
    Sun, Xiaoming
    Einkauf, Kevin B [ORCID]
    Chevalier, Joshua M [ORCID]
    Chen, Samantha M Y [ORCID]
    Hua, Stephane [ORCID]
    Rhee, Ben
    Chang, Kaylee
    Blackmer, Jane E
    Osborn, Matthew
    Peluso, Michael J
    Hoh, Rebecca
    Somsouk, Ma
    Milush, Jeffrey
    Bertagnolli, Lynn N
    Sweet, Sarah E
    Varriale, Joseph A
    Burbelo, Peter D
    Chun, Tae-Wook
    Laird, Gregory M [ORCID]
    Serrao, Erik
    Engelman, Alan N
    Carrington,Mary [ORCID]
    Siliciano, Robert F
    Siliciano, Janet M
    Deeks, Steven G [ORCID]
    Walker, Bruce D [ORCID]
    Lichterfeld, Mathias
    Yu, Xu G [ORCID]

  2. Author Address

    Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA., Infectious Disease Division, Brigham and Women 39;s Hospital, Boston, MA, USA., Department of Medicine, University of California at San Francisco, San Francisco, CA, USA., Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Dental Clinical Research Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA., National Institute of Allergies and Infectious Diseases, Bethesda, MD, USA., Accelevir Diagnostics, Baltimore, MD, USA., Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA., Department of Medicine, Harvard Medical School, Boston, MA, USA., Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Howard Hughes Medical Institute, Chevy Chase, MD, USA., Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA., Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA., Broad Institute of MIT and Harvard, Cambridge, MA, USA., Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA. xyu@mgh.harvard.edu., Infectious Disease Division, Brigham and Women 39;s Hospital, Boston, MA, USA. xyu@mgh.harvard.edu.,
    1. Year: 2020
    2. Date: Aug 26
    3. Epub Date: 2020 08 26
  2. Journal: Nature
  4. Type of Article: Article
  5. ISSN: 0028-0836
  1. Abstract:

    Sustained, drug-free control of HIV-1 replication is naturally achieved in less than 0.5% of infected individuals (here termed 39;elite controllers 39;), despite the presence of a replication-competent viral reservoir1. Inducing such an ability to spontaneously maintain undetectable plasma viraemia is a major objective of HIV-1 160;cure 160;research, but the characteristics of proviral reservoirs in elite controllers remain to be determined. Here, using next-generation sequencing of near-full-length single HIV-1 genomes and corresponding 160;chromosomal integration sites, we show that the proviral reservoirs of elite controllers frequently consist of oligoclonal to near-monoclonal clusters of intact proviral sequences. In contrast to individuals treated with long-term antiretroviral therapy, intact proviral sequences from elite controllers were integrated at highly distinct sites in the human genome and were preferentially located in centromeric satellite DNA or in Kr 252;ppel-associated box domain-containing zinc finger genes on chromosome 19, both of which are associated with heterochromatin features. Moreover, the integration sites of intact proviral sequences from elite controllers showed an increased distance to transcriptional start sites and accessible chromatin of the host genome and were enriched in repressive chromatin marks. These data suggest that a distinct configuration of the proviral reservoir represents a structural correlate of natural viral control, and that the quality, rather than the quantity, of viral reservoirs can be an important distinguishing feature for a functional cure of HIV-1 infection. Moreover, in one elite controller, we were unable to detect intact proviral sequences despite analysing more than 1.5 160;billion peripheral blood mononuclear cells, which raises the possibility that a sterilizing cure of HIV-1 infection, which has previously been observed only following allogeneic haematopoietic stem cell transplantation2,3, may be feasible in rare instances.

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External Sources

  1. View Full Text
  2. DOI: 10.1038/s41586-020-2651-8
  3. PMID: 32848246
  4. View record in Web of Science®
  5. WOS: 000563193800005
  6. PII : 10.1038/s41586-020-2651-8

Library Notes

  1. Fiscal Year: FY2019-2020
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