Functional landscape of SARS-CoV-2 cellular restriction.
Animals
Antigens, CD
/ chemistry
Binding Sites
Cell Line, Tumor
Chlorocebus aethiops
Endoplasmic Reticulum
/ genetics
GPI-Linked Proteins
/ chemistry
Gene Expression Regulation
Golgi Apparatus
/ genetics
HEK293 Cells
Host-Pathogen Interactions
/ genetics
Humans
Immunity, Innate
Interferon Regulatory Factors
/ classification
Interferon Type I
/ genetics
Molecular Docking Simulation
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
SARS-CoV-2
/ genetics
Signal Transduction
Vero Cells
Viral Proteins
/ chemistry
Virus Internalization
Virus Release
/ genetics
Virus Replication
/ genetics
BST2
ISG
Orf7a
SARS-CoV-2
innate immunity
interferon
viral evasion
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
17 06 2021
17 06 2021
Historique:
received:
17
09
2020
revised:
01
02
2021
accepted:
07
04
2021
pubmed:
1
5
2021
medline:
29
6
2021
entrez:
30
4
2021
Statut:
ppublish
Résumé
A deficient interferon (IFN) response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been implicated as a determinant of severe coronavirus disease 2019 (COVID-19). To identify the molecular effectors that govern IFN control of SARS-CoV-2 infection, we conducted a large-scale gain-of-function analysis that evaluated the impact of human IFN-stimulated genes (ISGs) on viral replication. A limited subset of ISGs were found to control viral infection, including endosomal factors inhibiting viral entry, RNA binding proteins suppressing viral RNA synthesis, and a highly enriched cluster of endoplasmic reticulum (ER)/Golgi-resident ISGs inhibiting viral assembly/egress. These included broad-acting antiviral ISGs and eight ISGs that specifically inhibited SARS-CoV-2 and SARS-CoV-1 replication. Among the broad-acting ISGs was BST2/tetherin, which impeded viral release and is antagonized by SARS-CoV-2 Orf7a protein. Overall, these data illuminate a set of ISGs that underlie innate immune control of SARS-CoV-2/SARS-CoV-1 infection, which will facilitate the understanding of host determinants that impact disease severity and offer potential therapeutic strategies for COVID-19.
Identifiants
pubmed: 33930332
pii: S1097-2765(21)00313-0
doi: 10.1016/j.molcel.2021.04.008
pmc: PMC8043580
pii:
doi:
Substances chimiques
Antigens, CD
0
BST2 protein, human
0
GPI-Linked Proteins
0
Interferon Regulatory Factors
0
Interferon Type I
0
ORF7a protein, SARS-CoV-2
0
Viral Proteins
0
Banques de données
GEO
['GSE156295']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2656-2668.e8Subventions
Organisme : NIGMS NIH HHS
ID : P41 GM103504
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI135990
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI163912
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007476
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA030199
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001422
Pays : United States
Organisme : NIAID NIH HHS
ID : F31 AI141111
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI118610
Pays : United States
Commentaires et corrections
Type : UpdateOf
Type : CommentIn
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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