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Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8+ cells

  1. Author:
    McBrien, Julia Bergild
    Mavigner, Maud
    Franchitti, Lavinia
    Smith, S Abigail
    White, Erick
    Tharp, Gregory K
    Walum, Hasse
    Busman-Suhay, Kathleen
    Aguilera-Sandoval, Christian R
    Thayer, William O
    Spagnuolo, Rae Ann
    Kovarova, Martina
    Wahl, Angela
    Cervasi, Barbara
    Margolis, David M
    Vanderford, Thomas H
    Carnathan, Diane G
    Paiardini, Mirko
    Lifson,Jeffrey
    Lee, John H
    Safrit, Jeffrey T
    Bosinger, Steven E
    Estes, Jacob D
    Derdeyn, Cynthia A
    Garcia, J Victor
    Kulpa, Deanna A
    Chahroudi, Ann
    Silvestri, Guido

  2. Author Address

    Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA., Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA., Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA., International Center for the Advancement of Translational Science, Division of Infectious Diseases, Center for AIDS Research, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., University of North Carolina HIV Cure Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA., AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., NantKwest, Culver City, CA, USA., Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA., Emory + Children 39;s Center for Childhood Infections and Vaccines, Atlanta, GA, USA., Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA. gsilves@emory.edu., Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA. gsilves@emory.edu.,
    1. Year: 2020
    2. Date: Jan 22
    3. Epub Date: 2020 01 22
  2. Journal: Nature
  4. Type of Article: Article
  5. ISSN: 0028-0836
  1. Abstract:

    Human immunodeficiency virus (HIV) persists indefinitely in individuals with HIV who receive antiretroviral therapy (ART) 160;owing to a reservoir of latently infected cells that contain replication-competent virus1-4. Here, to better understand the mechanisms responsible for latency persistence and reversal, we used the interleukin-15 superagonist N-803 in conjunction with the depletion of CD8+ lymphocytes in ART-treated macaques infected with simian immunodeficiency virus (SIV). Although N-803 alone did not reactivate 160;virus production, its administration after the depletion of CD8+ lymphocytes in conjunction with ART treatment induced robust and persistent reactivation of the virus in vivo. We found viraemia of more than 60 160;copies per ml in all macaques (n 160;= 160;14; 100%) and in 41 out of a total of 56 samples (73.2%) that were collected each week after N-803 administration. Notably, concordant results were obtained in ART-treated HIV-infected humanized mice. In addition, we observed that co-culture with CD8+ T cells blocked the in vitro latency-reversing effect of N-803 on primary human CD4+ T cells that were latently infected with HIV. These results advance our understanding of the mechanisms responsible for latency reversal and lentivirus reactivation during ART-suppressed infection.

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External Sources

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  2. DOI: 10.1038/s41586-020-1946-0
  3. PMID: 31969705
  4. View record in Web of Science®
  5. WOS: 000508801100008
  6. PII : 10.1038/s41586-020-1946-0

Library Notes

  1. Fiscal Year: FY2019-2020
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