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Latency reversal plus natural killer cells diminish HIV reservoir in vivo

Author

Listed:
  • Jocelyn T. Kim

    (University of California Los Angeles)

  • Tian-Hao Zhang

    (University of California Los Angeles)

  • Camille Carmona

    (University of California Los Angeles)

  • Bryanna Lee

    (University of California Los Angeles)

  • Christopher S. Seet

    (University of California Los Angeles)

  • Matthew Kostelny

    (University of California Los Angeles)

  • Nisarg Shah

    (University of California Los Angeles)

  • Hongying Chen

    (University of California Los Angeles)

  • Kylie Farrell

    (University of California Los Angeles)

  • Mohamed S. A. Soliman

    (University of California Los Angeles)

  • Melanie Dimapasoc

    (University of California Los Angeles)

  • Michelle Sinani

    (University of California Los Angeles)

  • Kenia Yazmin Reyna Blanco

    (University of California Los Angeles)

  • David Bojorquez

    (University of California Los Angeles)

  • Hong Jiang

    (University of California)

  • Yuan Shi

    (University of California)

  • Yushen Du

    (University of California)

  • Natalia L. Komarova

    (University of California, Irvine)

  • Dominik Wodarz

    (University of California, Irvine)

  • Paul A. Wender

    (Stanford University)

  • Matthew D. Marsden

    (University of California, Irvine)

  • Ren Sun

    (University of California
    The University of Hong Kong)

  • Jerome A. Zack

    (University of California Los Angeles
    University of California Los Angeles)

Abstract

HIV is difficult to eradicate due to the persistence of a long-lived reservoir of latently infected cells. Previous studies have shown that natural killer cells are important to inhibiting HIV infection, but it is unclear whether the administration of natural killer cells can reduce rebound viremia when anti-retroviral therapy is discontinued. Here we show the administration of allogeneic human peripheral blood natural killer cells delays viral rebound following interruption of anti-retroviral therapy in humanized mice infected with HIV-1. Utilizing genetically barcoded virus technology, we show these natural killer cells efficiently reduced viral clones rebounding from latency. Moreover, a kick and kill strategy comprised of the protein kinase C modulator and latency reversing agent SUW133 and allogeneic human peripheral blood natural killer cells during anti-retroviral therapy eliminated the viral reservoir in a subset of mice. Therefore, combinations utilizing latency reversal agents with targeted cellular killing agents may be an effective approach to eradicating the viral reservoir.

Suggested Citation

  • Jocelyn T. Kim & Tian-Hao Zhang & Camille Carmona & Bryanna Lee & Christopher S. Seet & Matthew Kostelny & Nisarg Shah & Hongying Chen & Kylie Farrell & Mohamed S. A. Soliman & Melanie Dimapasoc & Mic, 2022. "Latency reversal plus natural killer cells diminish HIV reservoir in vivo," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27647-0
    DOI: 10.1038/s41467-021-27647-0
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    References listed on IDEAS

    as
    1. Tae-Wook Chun & Richard T. Davey & Delphine Engel & H. Clifford Lane & Anthony S. Fauci, 1999. "Re-emergence of HIV after stopping therapy," Nature, Nature, vol. 401(6756), pages 874-875, October.
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