HIV-1 Vpu restricts Fc-mediated effector functions in vivo.
ADCC
CD4 mimetics
CP: Immunology
Env
Fc-effector functions
HIV-1
Vpu
broadly neutralizing antibodies
humanized mice
immune evasion
non-neutralizing antibodies
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
08 11 2022
08 11 2022
Historique:
received:
01
03
2022
revised:
02
09
2022
accepted:
17
10
2022
entrez:
9
11
2022
pubmed:
10
11
2022
medline:
15
11
2022
Statut:
ppublish
Résumé
Non-neutralizing antibodies (nnAbs) can eliminate HIV-1-infected cells via antibody-dependent cellular cytotoxicity (ADCC) and were identified as a correlate of protection in the RV144 vaccine trial. Fc-mediated effector functions of nnAbs were recently shown to alter the course of HIV-1 infection in vivo using a vpu-defective virus. Since Vpu is known to downregulate cell-surface CD4, which triggers conformational changes in the viral envelope glycoprotein (Env), we ask whether the lack of Vpu expression was linked to the observed nnAbs activity. We find that restoring Vpu expression greatly reduces nnAb recognition of infected cells, rendering them resistant to ADCC. Moreover, administration of nnAbs in humanized mice reduces viral loads only in animals infected with a vpu-defective but not with a wild-type virus. CD4-mimetics administration, known to "open" Env and expose nnAb epitopes, renders wild-type viruses sensitive to nnAbs Fc-effector functions. This work highlights the importance of Vpu-mediated evasion of humoral responses.
Identifiants
pubmed: 36351384
pii: S2211-1247(22)01495-4
doi: 10.1016/j.celrep.2022.111624
pmc: PMC9703018
mid: NIHMS1848911
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
HIV Antibodies
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
Pagination
111624Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI144462
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI148379
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI150471
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI129769
Pays : United States
Organisme : NIGMS NIH HHS
ID : P01 GM056550
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI131251
Pays : United States
Organisme : NIAID NIH HHS
ID : P50 AI150464
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI116274
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI164562
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI150322
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI150590
Pays : United States
Organisme : NIAID NIH HHS
ID : R33 AI122384
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI145164
Pays : United States
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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