Anti‐ HIV ‐1 antibodies trigger non‐lytic complement deposition on infected cells

Jérémy Dufloo (1, 2) , Florence Guivel-Benhassine (1) , Julian Buchrieser (1) , Valérie Lorin (3) , Ludivine Grzelak (1) , Emilie Dupouy (1) , Guillaume Mestrallet (1) , Katia Bourdic (4, 5) , Olivier Lambotte (4, 5) , Hugo Mouquet (3, 6) , Timothée Bruel (1, 6) , Olivier Schwartz (1, 6)

1 CNRS-UMR3569 - Virus et Immunité - Virus and immunity
2 Université Paris Diderot, Sorbonne Paris Cité, Paris, France
3 Immunologie humorale - Humoral Immunology
4 IMVA-HB - Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes
5 Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre]
6 VRI - Vaccine Research Institute [Créteil, France]

The effect of anti-HIV-1 antibodies on complement activation at the surface of infected cells remains partly understood. Here, we show that a subset of anti-Envelope (Env) broadly neutralizing antibodies (bNAbs), targeting the CD4 binding site and the V3 loop, triggers C3 deposition and complement-dependent cytotoxicity (CDC) on Raji cells engineered to express high surface levels of HIV-1 Env. Primary CD4 T cells infected with laboratory-adapted or primary HIV-1 strains and treated with bNAbs are susceptible to C3 deposition but not to rapid CDC. The cellular protein CD59 and viral proteins Vpu and Nef protect infected cells from CDC mediated by bNAbs or by polyclonal IgGs from HIV-positive individuals. However, complement deposition accelerates the disappearance of infected cells within a few days of culture. Altogether, our results uncover the contribution of complement to the antiviral activity of anti-HIV-1 bNAbs.

Mots clés: HIV-1; broadly neutralizing antibodies; complement

Domaines: Sciences du Vivant [q-bio]

Jérémy Dufloo, Florence Guivel-Benhassine, Julian Buchrieser, Valérie Lorin, Ludivine Grzelak, et al.. Anti‐ HIV ‐1 antibodies trigger non‐lytic complement deposition on infected cells. EMBO Reports, 2019, 21 (2), pp.e49351. ⟨10.15252/embr.201949351⟩. ⟨pasteur-03239697⟩