Contributors: Virus et Immunité - Virus and immunity (CNRS-UMR3569); Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC); Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité); Immunologie humorale - Humoral Immunology; Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Trafic membranaire et Division cellulaire - Membrane Traffic and Cell Division; Hôpital Bretonneau; Centre Hospitalier Régional Universitaire de Tours (CHRU Tours); Plateforme IBISA de Microscopie Electronique [CHRU de Tours] (UNIV Tours); Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT); Vaccine Research Institute [Créteil, France] (VRI); Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12); O.S. is funded by Institut Pasteur, Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Sidaction, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), 'TIMTAMDEN' ANR-14-CE14-0029, 'CHIKV-Viro-Immuno' ANR-14-CE14-0015-01, and the Gilead HIV cure program. J.D. is funded by a Ph.D grant from the French Ministry of Higher Education and Research. H.M. is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69-01), INSERM, ANRS, and Gilead HIV cure program. C.P. was supported by an ANRS fellowship. A.E. and S.F. are funded by Institut Pasteur, CNRS, and ANRS (ANRS-21020 AP2020-2). P.R. is funded by INSERM, Université de Tours and ANRS.; ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010); ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010); ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014); ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014); ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010); Virus et Immunité - Virus and immunity; Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Vaccine Research Institute (VRI); Institut Pasteur; Agence Nationale de la Recherche (France); Ministére de l'Education Nationale de la Recherche et de la Technologie (France); Université de Tours
نبذة مختصرة : Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) are promising molecules for therapeutic or prophylactic interventions. Beyond neutralization, bNAbs exert Fc-dependent functions including antibody-dependent cellular cytotoxicity and activation of the complement. Here, we show that a subset of bNAbs targeting the CD4 binding site and the V1/V2 or V3 loops inhibit viral release from infected cells. We combined immunofluorescence, scanning electron microscopy, transmission electron microscopy and immunogold staining to reveal that some bNAbs form large aggregates of virions at the surface of infected cells. This activity correlates with the capacity of bNAbs to bind to Env at the cell surface and to neutralize cell-free viral particles. We further show that antibody bivalency is required for viral retention, and that aggregated virions are neutralized. We have thus identified an additional antiviral activity of bNAbs, which block HIV-1 release by tethering viral particles at the surface of infected cells.
O.S. is funded by Institut Pasteur, Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Sidaction, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), “TIMTAMDEN” ANR-14-CE14-0029, “CHIKV-Viro-Immuno” ANR-14-CE14-0015-01, and the Gilead HIV cure program. J.D. is funded by a Ph.D grant from the French Ministry of Higher Education and Research. H.M. is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69-01), INSERM, ANRS, and Gilead HIV cure program. C.P. was supported by an ANRS fellowship. A.E. and S.F. are funded by Institut Pasteur, CNRS, and ANRS (ANRS-21020 AP2020-2). P.R. is funded by INSERM, Université de Tours and ANRS.
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