Vaccinia E5 is a major inhibitor of the DNA sensor cGAS.
Mice, Inbred C57BL
Animals
Mice
Mice, Knockout
Female
Nucleotidyltransferases
/ immunology
Dendritic Cells
/ immunology
Vaccinia virus
/ pathogenicity
Virulence Factors
/ immunology
Ubiquitination
Viral Proteins
/ genetics
Proteasome Endopeptidase Complex
Interferon Type I
/ immunology
HEK293 Cells
Humans
Membrane Proteins
/ immunology
T-Lymphocytes
/ immunology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 05 2023
22 05 2023
Historique:
received:
02
06
2022
accepted:
05
05
2023
medline:
24
5
2023
pubmed:
23
5
2023
entrez:
22
5
2023
Statut:
epublish
Résumé
The DNA sensor cyclic GMP-AMP synthase (cGAS) is critical in host antiviral immunity. Vaccinia virus (VACV) is a large cytoplasmic DNA virus that belongs to the poxvirus family. How vaccinia virus antagonizes the cGAS-mediated cytosolic DNA-sensing pathway is not well understood. In this study, we screened 80 vaccinia genes to identify potential viral inhibitors of the cGAS/Stimulator of interferon gene (STING) pathway. We discovered that vaccinia E5 is a virulence factor and a major inhibitor of cGAS. E5 is responsible for abolishing cGAMP production during vaccinia virus (Western Reserve strain) infection of dendritic cells. E5 localizes to the cytoplasm and nucleus of infected cells. Cytosolic E5 triggers ubiquitination of cGAS and proteasome-dependent degradation via interacting with cGAS. Deleting the E5R gene from the Modified vaccinia virus Ankara (MVA) genome strongly induces type I IFN production by dendritic cells (DCs) and promotes DC maturation, and thereby improves antigen-specific T cell responses.
Identifiants
pubmed: 37217469
doi: 10.1038/s41467-023-38514-5
pii: 10.1038/s41467-023-38514-5
pmc: PMC10201048
doi:
Substances chimiques
cGAS protein, mouse
EC 2.7.7.-
Nucleotidyltransferases
EC 2.7.7.-
Virulence Factors
0
E5R protein, Vaccinia virus
0
Viral Proteins
0
Proteasome Endopeptidase Complex
EC 3.4.25.1
Interferon Type I
0
Sting1 protein, mouse
0
Membrane Proteins
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
2898Subventions
Organisme : NIAID NIH HHS
ID : K08 AI073736
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIAMS NIH HHS
ID : R03 AR068118
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM132111
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI095692
Pays : United States
Informations de copyright
© 2023. The Author(s).
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