dc.contributor.author | Yang, N | |
dc.contributor.author | Wang, Y | |
dc.contributor.author | Dai, P | |
dc.contributor.author | Li, T | |
dc.contributor.author | Zierhut, C | |
dc.contributor.author | Tan, A | |
dc.contributor.author | Zhang, T | |
dc.contributor.author | Xiang, JZ | |
dc.contributor.author | Ordureau, A | |
dc.contributor.author | Funabiki, H | |
dc.contributor.author | Chen, Z | |
dc.contributor.author | Deng, L | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2023-08-15T14:11:58Z | |
dc.date.available | 2023-08-15T14:11:58Z | |
dc.date.issued | 2023-05-22 | |
dc.identifier | 2898 | |
dc.identifier | 10.1038/s41467-023-38514-5 | |
dc.identifier.citation | Nature Communications, 2023, 14 (1), pp. 2898 - | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5939 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-023-38514-5 | |
dc.description.abstract | 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. | |
dc.format | Electronic | |
dc.format.extent | 2898 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.relation.ispartof | Nature Communications | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Mice, Inbred C57BL | |
dc.subject | Animals | |
dc.subject | Mice | |
dc.subject | Mice, Knockout | |
dc.subject | Female | |
dc.subject | Nucleotidyltransferases | |
dc.subject | Dendritic Cells | |
dc.subject | Vaccinia virus | |
dc.subject | Virulence Factors | |
dc.subject | Ubiquitination | |
dc.subject | Viral Proteins | |
dc.subject | Proteasome Endopeptidase Complex | |
dc.subject | Interferon Type I | |
dc.subject | HEK293 Cells | |
dc.subject | Humans | |
dc.subject | Membrane Proteins | |
dc.subject | T-Lymphocytes | |
dc.title | Vaccinia E5 is a major inhibitor of the DNA sensor cGAS. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-05-05 | |
dc.date.updated | 2023-08-15T14:11:11Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/s41467-023-38514-5 | |
rioxxterms.licenseref.startdate | 2023-05-22 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37217469 | |
pubs.issue | 1 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Genome Stability and Innate Immunity | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1038/s41467-023-38514-5 | |
pubs.volume | 14 | |
icr.researchteam | Genome Stab & Immunity | |
dc.contributor.icrauthor | Zierhut, Christian | |
icr.provenance | Deposited by Mr Arek Surman (impersonating Prof Robert Huddart) on 2023-08-15. Deposit type is initial. No. of files: 1. Files: Vaccinia E5 is a major inhibitor of the DNA sensor cGAS.pdf | |