title: Elimination of HIV-1-infected cells by broadly neutralizing antibodies.
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.
authors.affiliation: Virus and Immunity Unit, Department of Virology, Institut Pasteur, Paris 75015, France.|CNRS-URA 3015, Paris 75015, France.
authors.forename: Timothée
authors.initials: T
authors.lastname: Bruel
authors.affiliation: Virus and Immunity Unit, Department of Virology, Institut Pasteur, Paris 75015, France.|CNRS-URA 3015, Paris 75015, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Guivel-Benhassine
authors.affiliation: Virus and Immunity Unit, Department of Virology, Institut Pasteur, Paris 75015, France.|CNRS-URA 3015, Paris 75015, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Amraoui
authors.affiliation: Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris 75015, France.|CNRS-URA 1961, Paris 75015, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Malbec
authors.affiliation: Virus and Immunity Unit, Department of Virology, Institut Pasteur, Paris 75015, France.|CNRS-URA 3015, Paris 75015, France.
authors.forename: Léa
authors.initials: L
authors.lastname: Richard
authors.affiliation: Université Paris Sud, UMR-1184, Le Kremlin Bicêtre 94276, France.|CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT, Fontenay-aux-Roses 92260, France.|Inserm, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre 94276, France.|APHP, Service de Médecine Interne-Immunologie Clinique, Hôpitaux Universitaires Paris Sud, Le Kremlin Bicêtre 94276, France.
authors.forename: Katia
authors.initials: K
authors.lastname: Bourdic
authors.affiliation: Virus and Immunity Unit, Department of Virology, Institut Pasteur, Paris 75015, France.|CNRS-URA 3015, Paris 75015, France.
authors.forename: Daniel Aaron
authors.initials: DA
authors.lastname: Donahue
authors.affiliation: Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris 75015, France.|CNRS-URA 1961, Paris 75015, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Lorin
authors.affiliation: Virus and Immunity Unit, Department of Virology, Institut Pasteur, Paris 75015, France.|CNRS-URA 3015, Paris 75015, France.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Casartelli
authors.affiliation: Université Paris Sud, UMR-1184, Le Kremlin Bicêtre 94276, France.|CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT, Fontenay-aux-Roses 92260, France.|Inserm, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre 94276, France.|APHP, Service de Médecine Interne-Immunologie Clinique, Hôpitaux Universitaires Paris Sud, Le Kremlin Bicêtre 94276, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Noël
authors.affiliation: Université Paris Sud, UMR-1184, Le Kremlin Bicêtre 94276, France.|CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT, Fontenay-aux-Roses 92260, France.|Inserm, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre 94276, France.|APHP, Service de Médecine Interne-Immunologie Clinique, Hôpitaux Universitaires Paris Sud, Le Kremlin Bicêtre 94276, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambotte
authors.affiliation: Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris 75015, France.|CNRS-URA 1961, Paris 75015, France.
authors.forename: Hugo
authors.initials: H
authors.lastname: Mouquet
authors.affiliation: Virus and Immunity Unit, Department of Virology, Institut Pasteur, Paris 75015, France.|CNRS-URA 3015, Paris 75015, France.|Vaccine Research Institute, Creteil 94000, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000502:physiology*; D000914:Antibodies, Viral / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002460:Cell Line; D015497:HIV-1 / Q000502:physiology*; D006801:Humans
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral