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Nat Commun. 2016 Mar 3;7:10844. doi: 10.1038/ncomms10844.

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

Author information

1
Virus and Immunity Unit, Department of Virology, Institut Pasteur, Paris 75015, France.
2
CNRS-URA 3015, Paris 75015, France.
3
Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris 75015, France.
4
CNRS-URA 1961, Paris 75015, France.
5
Université Paris Sud, UMR-1184, Le Kremlin Bicêtre 94276, France.
6
CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT, Fontenay-aux-Roses 92260, France.
7
Inserm, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre 94276, France.
8
APHP, Service de Médecine Interne-Immunologie Clinique, Hôpitaux Universitaires Paris Sud, Le Kremlin Bicêtre 94276, France.
9
Vaccine Research Institute, Creteil 94000, France.

Abstract

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.

PMID:
26936020
PMCID:
PMC4782064
DOI:
10.1038/ncomms10844
[Indexed for MEDLINE]
Free PMC Article

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