Vaccinia E5 is a major inhibitor of the DNA sensor cGAS.
Date
2023-05-22ICR Author
Author
Yang, N
Wang, Y
Dai, P
Li, T
Zierhut, C
Tan, A
Zhang, T
Xiang, JZ
Ordureau, A
Funabiki, H
Chen, Z
Deng, L
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Mice, Inbred C57BL
Animals
Mice
Mice, Knockout
Female
Nucleotidyltransferases
Dendritic Cells
Vaccinia virus
Virulence Factors
Ubiquitination
Viral Proteins
Proteasome Endopeptidase Complex
Interferon Type I
HEK293 Cells
Humans
Membrane Proteins
T-Lymphocytes
Research team
Genome Stab & Immunity
Language
eng
Date accepted
2023-05-05
License start date
2023-05-22
Citation
Nature Communications, 2023, 14 (1), pp. 2898 -
Publisher
NATURE PORTFOLIO