CD4 Incorporation into HIV-1 Viral Particles Exposes Envelope Epitopes Recognized by CD4-Induced Antibodies.
Animals
Antibody-Dependent Cell Cytotoxicity
/ immunology
CD4 Antigens
/ immunology
CD4-Positive T-Lymphocytes
/ immunology
Cell Line
Dogs
Epitopes
/ immunology
HEK293 Cells
HIV Antibodies
/ immunology
HIV Envelope Protein gp120
/ metabolism
HIV Infections
/ virology
HIV Seropositivity
HIV-1
/ immunology
Humans
Protein Binding
/ immunology
Viral Envelope Proteins
/ immunology
Virion
/ metabolism
env Gene Products, Human Immunodeficiency Virus
/ immunology
CD4
CD4-induced antibodies
Env
Env conformation
HIV-1
cold inactivation
incorporation
neutralization
nonneutralizing antibodies
virus capture assay
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
15 11 2019
15 11 2019
Historique:
received:
20
08
2019
accepted:
29
08
2019
pubmed:
6
9
2019
medline:
21
7
2020
entrez:
6
9
2019
Statut:
epublish
Résumé
CD4 downregulation on infected cells is a highly conserved function of primate lentiviruses. It has been shown to positively impact viral replication by a variety of mechanisms, including enhanced viral release and infectivity, decrease of cell reinfection, and protection from antibody-dependent cellular cytotoxicity (ADCC), which is often mediated by antibodies that require CD4 to change envelope (Env) conformation. Here, we report that incorporation of CD4 into HIV-1 viral particles affects Env conformation resulting in the exposure of occluded epitopes recognized by CD4-induced antibodies. This translates into enhanced neutralization susceptibility by these otherwise nonneutralizing antibodies but is prevented by the HIV-1 Nef accessory protein. Altogether, these findings suggest that another functional consequence of Nef-mediated CD4 downregulation is the protection of viral particles from neutralization by commonly elicited CD4-induced antibodies.
Identifiants
pubmed: 31484748
pii: JVI.01403-19
doi: 10.1128/JVI.01403-19
pmc: PMC6819941
pii:
doi:
Substances chimiques
CD4 Antigens
0
Epitopes
0
HIV Antibodies
0
HIV Envelope Protein gp120
0
Viral Envelope Proteins
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 AI129769
Pays : United States
Organisme : NIAID NIH HHS
ID : R33 AI129017
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI124982
Pays : United States
Organisme : CIHR
ID : 352417
Pays : Canada
Organisme : NIAID NIH HHS
ID : R01 AI145547
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI116274
Pays : United States
Informations de copyright
Copyright © 2019 American Society for Microbiology.
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