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

Timothée Bruel (1) , Florence Guivel-Benhassine (1) , Sonia Amraoui (1) , Marine Malbec (2) , Léa Richard (1) , Katia Bourdic (3) , Daniel Aaron Donahue (1) , Valérie Lorin (2) , Nicoletta Casartelli (1) , Nicolas Noël (3) , Olivier Lambotte (3) , Hugo Mouquet (2) , Olivier Schwartz (1)

1 Virus et Immunité
2 Réponse humorale aux pathogènes
3 IMVA - U1184 - Immunologie des Maladies Virales et Autoimmunes

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.

Domaines: Sciences du Vivant [q-bio]

Timothée Bruel, Florence Guivel-Benhassine, Sonia Amraoui, Marine Malbec, Léa Richard, et al.. Elimination of HIV-1-infected cells by broadly neutralizing antibodies.. Nature Communications, 2015, 7, pp.10844. ⟨10.1038/ncomms10844⟩. ⟨pasteur-01372390⟩