Restriction factor screening identifies RABGAP1L-mediated disruption of endocytosis as a host antiviral defense.
CP: Immunology
CP: Microbiology
ISG
RABGAP1L
VPS33A
endocytosis
host defense
influenza
interferon
proximity labeling
siRNA screening
virus restriction
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
22 03 2022
22 03 2022
Historique:
received:
06
10
2021
revised:
31
01
2022
accepted:
01
03
2022
entrez:
23
3
2022
pubmed:
24
3
2022
medline:
31
3
2022
Statut:
ppublish
Résumé
Host interferons (IFNs) powerfully restrict viruses through the action of several hundred IFN-stimulated gene (ISG) products, many of which remain uncharacterized. Here, using RNAi screening, we identify several ISG restriction factors with previously undescribed contributions to IFN-mediated defense. Notably, RABGAP1L, a Tre2/Bub2/Cdc16 (TBC)-domain-containing protein involved in regulation of small membrane-bound GTPases, robustly potentiates IFN action against influenza A viruses (IAVs). Functional studies reveal that the catalytically active TBC domain of RABGAP1L promotes antiviral activity, and the RABGAP1L proximal interactome uncovered its association with proteins involved in endosomal sorting, maturation, and trafficking. In this regard, RABGAP1L overexpression is sufficient to disrupt endosomal function during IAV infection and restricts an early post-attachment, but pre-fusion, stage of IAV cell entry. Other RNA viruses that enter cells primarily via endocytosis are also impaired by RABGAP1L, while entry promiscuous SARS-CoV-2 is resistant. Our data highlight virus endocytosis as a key target for host defenses.
Identifiants
pubmed: 35320721
pii: S2211-1247(22)00290-X
doi: 10.1016/j.celrep.2022.110549
pmc: PMC8939003
pii:
doi:
Substances chimiques
Antiviral Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110549Informations de copyright
Copyright © 2022 The Author(s). 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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