Antibody-Induced Internalization of HIV-1 Env Proteins Limits Surface Expression of the Closed Conformation of Env.
Antibodies, Neutralizing
/ immunology
Antibody-Dependent Cell Cytotoxicity
/ immunology
CD4-Positive T-Lymphocytes
/ immunology
Gene Expression Regulation, Viral
/ genetics
HEK293 Cells
HIV Antibodies
/ immunology
HIV Infections
/ immunology
HIV Seropositivity
HIV-1
/ immunology
Humans
Molecular Conformation
Virus Internalization
env Gene Products, Human Immunodeficiency Virus
/ immunology
ADCC
Env
Env conformation
HIV-1
Internalization
bNAbs
dynamin
nonneutralizing antibodies
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
01 06 2019
01 06 2019
Historique:
received:
19
02
2019
accepted:
16
03
2019
pubmed:
22
3
2019
medline:
24
6
2020
entrez:
22
3
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30894474
pii: JVI.00293-19
doi: 10.1128/JVI.00293-19
pmc: PMC6532100
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
HIV Antibodies
0
env Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : P01 AI150471
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI095098
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI129769
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM116654
Pays : United States
Organisme : NIGMS NIH HHS
ID : P01 GM056550
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI120756
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI121135
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI098485
Pays : United States
Organisme : CIHR
ID : 352417
Pays : Canada
Organisme : NIAID NIH HHS
ID : R01 AI116274
Pays : United States
Informations de copyright
Copyright © 2019 American Society for Microbiology.
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