Vaccinia E5 is a major inhibitor of the DNA sensor cGAS Journal Article

   


Authors: Yang, N.; Wang, Y.; Dai, P.; Li, T.; Zierhut, C.; Tan, A.; Zhang, T.; Xiang, J. Z.; Ordureau, A.; Funabiki, H.; Chen, Z.; Deng, L.
Article Title: Vaccinia E5 is a major inhibitor of the DNA sensor cGAS
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. © 2023, The Author(s).
Keywords: genetics; metabolism; dna; vaccinia virus; innate immunity; immunity, innate; nucleotidyltransferase; vaccinia; nucleotidyltransferases; humans; human; modified vaccinia ankara virus
Journal Title: Nature Communications
Volume: 14
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2023-05-22
Start Page: 2898
Language: English
DOI: 10.1038/s41467-023-38514-5
PUBMED: 37217469
PROVIDER: scopus
PMCID: PMC10201048
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85159819111&doi=10.1038%2fs41467-023-38514-5&partnerID=40&md5=c064ca588da9739ccf0ac2e86c3312f9
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged via PDF -- MSK corresponding authors are Ning Yang and Liang Deng -- Export Date: 1 June 2023 -- Source: Scopus
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MSK Authors
  1. Liang Deng
    83 Deng
  2. Peihong Dai
    40 Dai
  3. Ning Yang
    25 Yang
  4. Yi Wang
    16 Wang
  5. Alban Simon Georges Ordureau
    16 Ordureau
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