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J Virol. 2019 May 15;93(11). pii: e00293-19. doi: 10.1128/JVI.00293-19. Print 2019 Jun 1.

Antibody-Induced Internalization of HIV-1 Env Proteins Limits Surface Expression of the Closed Conformation of Env.

Author information

1
Centre de Recherche du CHUM, Montreal, Quebec, Canada.
2
Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
3
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA.
4
Infectious Diseases Division, Department of Medicine of Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
5
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada.
6
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA.
7
Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin, USA.
8
Centre de Recherche du CHUM, Montreal, Quebec, Canada andres.finzi@umontreal.ca.

Abstract

To minimize immune responses against infected cells, HIV-1 limits the surface expression of its envelope glycoprotein (Env). Here, we demonstrate that this mechanism is specific for the Env conformation and affects the efficiency of antibody-dependent cellular cytotoxicity (ADCC). Using flow cytometry and confocal microscopy, we show that broadly neutralizing antibodies (bNAbs) targeting the "closed" conformation of Env induce its internalization from the surface. In contrast, non-neutralizing antibodies (nNAbs) are displayed on the cell surface for prolonged period of times. The bNAb-induced Env internalization can be decreased by blocking dynamin function, which translates into higher susceptibilities of infected cells to ADCC. Our results suggest that antibody-mediated Env internalization is a mechanism used by HIV-1 to evade immune responses against the "closed" conformation of Env expressed on HIV-1-infected cells.IMPORTANCE HIV-1 has evolved to acquire several strategies to limit the exposure of its envelope glycoproteins (Env) on the surface of infected cells. In this study, we show that antibody-induced Env internalization is conformation specific and reduces the susceptibility of infected cells to antibody-dependent cellular cytotoxicity (ADCC). Thus, a better understanding of this mechanism might help develop antibodies with improved capacities to mediate ADCC.

KEYWORDS:

ADCC; Env; Env conformation; HIV-1; Internalization; bNAbs; dynamin; nonneutralizing antibodies

PMID:
30894474
PMCID:
PMC6532100
[Available on 2019-11-15]
DOI:
10.1128/JVI.00293-19

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