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

Jérémy Dufloo; Florence Guivel-Benhassine; Julian Buchrieser; Valérie Lorin; Ludivine Grzelak; Emilie Dupouy; Guillaume Mestrallet; Katia Bourdic; Olivier Lambotte; Hugo Mouquet; Timothée Bruel; Olivier Schwartz

doi:10.15252/embr.201949351

Journal articles

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, 6} Olivier Lambotte ^{4, 5, 6} Hugo Mouquet ^{3, 7} Timothée Bruel ^{1, 7, *} Olivier Schwartz ^{1, 7, *}

* Corresponding author

1 Virus et Immunité

2 Université Paris Diderot, Sorbonne Paris Cité, Paris, France

3 Immunologie humorale - Humoral Immunology

4 IMVA - U1184 - Immunologie des Maladies Virales et Autoimmunes

5 IDMIT - Infectious Diseases Models for Innovative Therapies

6 Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre]

7 VRI - Vaccine Research Institute

Abstract : 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.

Keywords : HIV-1 broadly neutralizing antibodies complement

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Microbiology and Parasitology / Virology

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Submitted on : Tuesday, June 2, 2020 - 9:58:54 AM
Last modification on : Wednesday, October 14, 2020 - 4:20:41 AM

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

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

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