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A quantitative approach for measuring the reservoir of latent HIV-1 proviruses

Author

Listed:
  • Katherine M. Bruner

    (Johns Hopkins University School of Medicine
    University of Texas)

  • Zheng Wang

    (Johns Hopkins University School of Medicine)

  • Francesco R. Simonetti

    (Johns Hopkins University School of Medicine)

  • Alexandra M. Bender

    (Johns Hopkins University School of Medicine)

  • Kyungyoon J. Kwon

    (Johns Hopkins University School of Medicine)

  • Srona Sengupta

    (Johns Hopkins University School of Medicine)

  • Emily J. Fray

    (Johns Hopkins University School of Medicine)

  • Subul A. Beg

    (Johns Hopkins University School of Medicine)

  • Annukka A. R. Antar

    (Johns Hopkins University School of Medicine)

  • Katharine M. Jenike

    (Johns Hopkins University School of Medicine)

  • Lynn N. Bertagnolli

    (Johns Hopkins University School of Medicine)

  • Adam A. Capoferri

    (Johns Hopkins University School of Medicine)

  • Joshua T. Kufera

    (Johns Hopkins University School of Medicine)

  • Andrew Timmons

    (Johns Hopkins University School of Medicine)

  • Christopher Nobles

    (University of Pennsylvania Perelman School of Medicine)

  • John Gregg

    (University of Pennsylvania Perelman School of Medicine)

  • Nikolas Wada

    (Johns Hopkins Bloomberg School of Public Health)

  • Ya-Chi Ho

    (Johns Hopkins University School of Medicine
    Yale School of Medicine)

  • Hao Zhang

    (Johns Hopkins Bloomberg School of Public Health)

  • Joseph B. Margolick

    (Johns Hopkins Bloomberg School of Public Health)

  • Joel N. Blankson

    (Johns Hopkins University School of Medicine)

  • Steven G. Deeks

    (University of California San Francisco)

  • Frederic D. Bushman

    (University of Pennsylvania Perelman School of Medicine)

  • Janet D. Siliciano

    (Johns Hopkins University School of Medicine)

  • Gregory M. Laird

    (Accelevir Diagnostics)

  • Robert F. Siliciano

    (Johns Hopkins University School of Medicine
    Howard Hughes Medical Institute)

Abstract

A stable latent reservoir for HIV-1 in resting CD4+ T cells is the principal barrier to a cure1–3. Curative strategies that target the reservoir are being tested4,5 and require accurate, scalable reservoir assays. The reservoir was defined with quantitative viral outgrowth assays for cells that release infectious virus after one round of T cell activation1. However, these quantitative outgrowth assays and newer assays for cells that produce viral RNA after activation6 may underestimate the reservoir size because one round of activation does not induce all proviruses7. Many studies rely on simple assays based on polymerase chain reaction to detect proviral DNA regardless of transcriptional status, but the clinical relevance of these assays is unclear, as the vast majority of proviruses are defective7–9. Here we describe a more accurate method of measuring the HIV-1 reservoir that separately quantifies intact and defective proviruses. We show that the dynamics of cells that carry intact and defective proviruses are different in vitro and in vivo. These findings have implications for targeting the intact proviruses that are a barrier to curing HIV infection.

Suggested Citation

  • Katherine M. Bruner & Zheng Wang & Francesco R. Simonetti & Alexandra M. Bender & Kyungyoon J. Kwon & Srona Sengupta & Emily J. Fray & Subul A. Beg & Annukka A. R. Antar & Katharine M. Jenike & Lynn N, 2019. "A quantitative approach for measuring the reservoir of latent HIV-1 proviruses," Nature, Nature, vol. 566(7742), pages 120-125, February.
  • Handle: RePEc:nat:nature:v:566:y:2019:i:7742:d:10.1038_s41586-019-0898-8
    DOI: 10.1038/s41586-019-0898-8
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    Citations

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    Cited by:

    1. Eva M. Stevenson & Sandra Terry & Dennis Copertino & Louise Leyre & Ali Danesh & Jared Weiler & Adam R. Ward & Pragya Khadka & Evan McNeil & Kevin Bernard & Itzayana G. Miller & Grant B. Ellsworth & C, 2022. "SARS CoV-2 mRNA vaccination exposes latent HIV to Nef-specific CD8+ T-cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Catherine DeMarino & Julia Denniss & Maria Cowen & Gina Norato & Devon K. Dietrich & Lisa Henderson & Elyse Gollomp & Joseph Snow & Darshan Pandya & Bryan Smith & Avindra Nath, 2024. "HIV-1 RNA in extracellular vesicles is associated with neurocognitive outcomes," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    3. Caroline Dufour & Corentin Richard & Marion Pardons & Marta Massanella & Antoine Ackaoui & Ben Murrell & Bertrand Routy & Réjean Thomas & Jean-Pierre Routy & Rémi Fromentin & Nicolas Chomont, 2023. "Phenotypic characterization of single CD4+ T cells harboring genetically intact and inducible HIV genomes," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Miriam Rosás-Umbert & Jesper D. Gunst & Marie H. Pahus & Rikke Olesen & Mariane Schleimann & Paul W. Denton & Victor Ramos & Adam Ward & Natalie N. Kinloch & Dennis C. Copertino & Tuixent Escribà & An, 2022. "Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8+ T cell immunity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    5. González, Ramón E.R. & Figueirêdo, P.H. & Coutinho, S., 2020. "Dynamics of HIV Infection: An entropic–energetic view," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 551(C).
    6. Daniel B. Reeves & Christian Gaebler & Thiago Y. Oliveira & Michael J. Peluso & Joshua T. Schiffer & Lillian B. Cohn & Steven G. Deeks & Michel C. Nussenzweig, 2023. "Impact of misclassified defective proviruses on HIV reservoir measurements," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    7. Daniel B. Reeves & Charline Bacchus-Souffan & Mark Fitch & Mohamed Abdel-Mohsen & Rebecca Hoh & Haelee Ahn & Mars Stone & Frederick Hecht & Jeffrey Martin & Steven G. Deeks & Marc K. Hellerstein & Jos, 2023. "Estimating the contribution of CD4 T cell subset proliferation and differentiation to HIV persistence," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    8. Aliu Oguntade Fatai & Raymond Osi Alenoghena, 2024. "The Role of Deposit Growth in The Productivity of Deposit Money Banks in Nigeria: Case Study of Union and Wema Banks in Lagos State," International Journal of Research and Scientific Innovation, International Journal of Research and Scientific Innovation (IJRSI), vol. 10(12), pages 234-246, January.
    9. Guinevere Q. Lee & Pragya Khadka & Sarah N. Gowanlock & Dennis C. Copertino & Maggie C. Duncan & F. Harrison Omondi & Natalie N. Kinloch & Jingo Kasule & Taddeo Kityamuweesi & Paul Buule & Samiri Jami, 2024. "HIV-1 subtype A1, D, and recombinant proviral genome landscapes during long-term suppressive therapy," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    10. Maria Pino & Amélie Pagliuzza & M. Betina Pampena & Claire Deleage & Elise G. Viox & Kevin Nguyen & Inbo Shim & Adam Zhang & Justin L. Harper & Sadia Samer & Colin T. King & Barbara Cervasi & Kiran P., 2022. "Limited impact of fingolimod treatment during the initial weeks of ART in SIV-infected rhesus macaques," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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