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Elimination of HIV-1-infected cells by broadly neutralizing antibodies

Author

Listed:
  • Timothée Bruel

    (Virus and Immunity Unit, Institut Pasteur
    CNRS-URA 3015)

  • Florence Guivel-Benhassine

    (Virus and Immunity Unit, Institut Pasteur
    CNRS-URA 3015)

  • Sonia Amraoui

    (Virus and Immunity Unit, Institut Pasteur
    CNRS-URA 3015)

  • Marine Malbec

    (Laboratory of Humoral Response to Pathogens, Institut Pasteur
    CNRS-URA 1961)

  • Léa Richard

    (Virus and Immunity Unit, Institut Pasteur
    CNRS-URA 3015)

  • Katia Bourdic

    (Université Paris Sud, UMR-1184
    CEA, DSV/iMETI, IDMIT
    Inserm, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases
    APHP, Service de Médecine Interne–Immunologie Clinique, Hôpitaux Universitaires Paris Sud)

  • Daniel Aaron Donahue

    (Virus and Immunity Unit, Institut Pasteur
    CNRS-URA 3015)

  • Valérie Lorin

    (Laboratory of Humoral Response to Pathogens, Institut Pasteur
    CNRS-URA 1961)

  • Nicoletta Casartelli

    (Virus and Immunity Unit, Institut Pasteur
    CNRS-URA 3015)

  • Nicolas Noël

    (Université Paris Sud, UMR-1184
    CEA, DSV/iMETI, IDMIT
    Inserm, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases
    APHP, Service de Médecine Interne–Immunologie Clinique, Hôpitaux Universitaires Paris Sud)

  • Olivier Lambotte

    (Université Paris Sud, UMR-1184
    CEA, DSV/iMETI, IDMIT
    Inserm, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases
    APHP, Service de Médecine Interne–Immunologie Clinique, Hôpitaux Universitaires Paris Sud)

  • Hugo Mouquet

    (Laboratory of Humoral Response to Pathogens, Institut Pasteur
    CNRS-URA 1961)

  • Olivier Schwartz

    (Virus and Immunity Unit, Institut Pasteur
    CNRS-URA 3015
    Vaccine Research Institute)

Abstract

The Fc region of HIV-1 Env-specific broadly neutralizing antibodies (bNAbs) is required for suppressing viraemia, through mechanisms which remain poorly understood. Here, we identify bNAbs that exert antibody-dependent cellular cytotoxicity (ADCC) in cell culture and kill HIV-1-infected lymphocytes through natural killer (NK) engagement. These antibodies target the CD4-binding site, the glycans/V3 and V1/V2 loops on gp120, or the gp41 moiety. The landscape of Env epitope exposure at the surface and the sensitivity of infected cells to ADCC vary considerably between viral strains. Efficient ADCC requires sustained cell surface binding of bNAbs to Env, and combining bNAbs allows a potent killing activity. Furthermore, reactivated infected cells from HIV-positive individuals expose heterogeneous Env epitope patterns, with levels that are often but not always sufficient to trigger killing by bNAbs. Our study delineates the parameters controlling ADCC activity of bNAbs, and supports the use of the most potent antibodies to clear the viral reservoir.

Suggested Citation

  • Timothée Bruel & Florence Guivel-Benhassine & Sonia Amraoui & Marine Malbec & Léa Richard & Katia Bourdic & Daniel Aaron Donahue & Valérie Lorin & Nicoletta Casartelli & Nicolas Noël & Olivier Lambott, 2016. "Elimination of HIV-1-infected cells by broadly neutralizing antibodies," Nature Communications, Nature, vol. 7(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10844
    DOI: 10.1038/ncomms10844
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    Cited by:

    1. Luis M. Molinos-Albert & Valérie Lorin & Valérie Monceaux & Sylvie Orr & Asma Essat & Jérémy Dufloo & Olivier Schwartz & Christine Rouzioux & Laurence Meyer & Laurent Hocqueloux & Asier Sáez-Cirión & , 2022. "Transient viral exposure drives functionally-coordinated humoral immune responses in HIV-1 post-treatment controllers," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Karunasinee Suphaphiphat & Delphine Desjardins & Valérie Lorin & Nastasia Dimant & Kawthar Bouchemal & Laetitia Bossevot & Maxence Galpin-Lebreau & Nathalie Dereuddre-Bosquet & Hugo Mouquet & Roger Gr, 2023. "Mucosal application of the broadly neutralizing antibody 10-1074 protects macaques from cell-associated SHIV vaginal exposure," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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