Varicella-Zoster virus ORF9 is an antagonist of the DNA sensor cGAS.
DNA sensing
ORF9
Varicella-Zoster virus
cGAS
phase separation
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
18 07 2022
18 07 2022
Historique:
revised:
04
05
2022
received:
15
07
2021
accepted:
09
05
2022
pubmed:
8
6
2022
medline:
20
7
2022
entrez:
7
6
2022
Statut:
ppublish
Résumé
Varicella-Zoster virus (VZV) causes chickenpox and shingles. Although the infection is associated with severe morbidity in some individuals, molecular mechanisms that determine innate immune responses remain poorly defined. We found that the cGAS/STING DNA sensing pathway was required for type I interferon (IFN) induction during VZV infection and that recognition of VZV by cGAS restricted its replication. Screening of a VZV ORF expression library identified the essential VZV tegument protein ORF9 as a cGAS antagonist. Ectopically or virally expressed ORF9 bound to endogenous cGAS leading to reduced type I IFN responses to transfected DNA. Confocal microscopy revealed co-localisation of cGAS and ORF9. ORF9 and cGAS also interacted directly in a cell-free system and phase-separated together with DNA. Furthermore, ORF9 inhibited cGAMP production by cGAS. Taken together, these results reveal the importance of the cGAS/STING DNA sensing pathway for VZV recognition and identify a VZV immune antagonist that partially but directly interferes with DNA sensing via cGAS.
Identifiants
pubmed: 35670106
doi: 10.15252/embj.2021109217
pmc: PMC9289529
doi:
Substances chimiques
Interferon Type I
0
Membrane Proteins
0
STING1 protein, human
0
Viral Proteins
0
DNA
9007-49-2
Nucleotidyltransferases
EC 2.7.7.-
cGAS protein, human
EC 2.7.7.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e109217Subventions
Organisme : Wellcome Trust
ID : 100954
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12025
Pays : United Kingdom
Organisme : NEI NIH HHS
ID : T32 EY017271
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_00008/8
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12009
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : R56 NS064022
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NEI NIH HHS
ID : P30 EY008098
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS064022
Pays : United States
Informations de copyright
© 2022 The Authors. Published under the terms of the CC BY 4.0 license.
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