Broadly neutralizing anti-HIV-1 antibodies tether viral particles at the surface of infected cells

Jérémy Dufloo (1, 2) , Cyril Planchais (3) , Stéphane Frémont (4) , Valerie Lorin (3) , Florence Guivel-Benhassine (1) , Karl Stefic (5) , Nicoletta Casartelli (1) , Arnaud Echard (4) , Philippe Roingeard (6) , Hugo Mouquet (3) , Olivier Schwartz (1, 7) , Timothée Bruel (1, 7)

1 CNRS-UMR3569 - Virus et Immunité - Virus and immunity
2 ED562 - BioSPC - École Doctorale Bio Sorbonne Paris Cité [Paris]
3 Immunologie humorale - Humoral Immunology
4 Trafic membranaire et Division cellulaire - Membrane Traffic and Cell Division
5 Hôpital Bretonneau
6 UNIV Tours - Plateforme IBISA de Microscopie Electronique [CHRU de Tours]
7 VRI - Vaccine Research Institute

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.

Domains: Virology

Jérémy Dufloo, Cyril Planchais, Stéphane Frémont, Valerie Lorin, Florence Guivel-Benhassine, et al.. Broadly neutralizing anti-HIV-1 antibodies tether viral particles at the surface of infected cells. Nature Communications, 2022, 13 (1), pp.630. ⟨10.1038/s41467-022-28307-7⟩. ⟨pasteur-03654220⟩