Title | Vaccinia E5 is a major inhibitor of the DNA sensor cGAS. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Yang N, Wang Y, Dai P, Li T, Zierhut C, Tan A, Zhang T, Xiang JZhaoying, Ordureau A, Funabiki H, Chen Z, Deng L |
Journal | Nat Commun |
Volume | 14 |
Issue | 1 |
Pagination | 2898 |
Date Published | 2023 May 22 |
ISSN | 2041-1723 |
Keywords | Animals, Dendritic Cells, Female, HEK293 Cells, Humans, Interferon Type I, Membrane Proteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Nucleotidyltransferases, Proteasome Endopeptidase Complex, T-Lymphocytes, Ubiquitination, Vaccinia virus, Viral Proteins, Virulence Factors |
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. |
DOI | 10.1038/s41467-023-38514-5 |
Alternate Journal | Nat Commun |
PubMed ID | 37217469 |
PubMed Central ID | PMC10201048 |
Grant List | K08 AI073736 / AI / NIAID NIH HHS / United States / HHMI / Howard Hughes Medical Institute / United States R03 AR068118 / AR / NIAMS NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States R35 GM132111 / GM / NIGMS NIH HHS / United States R56 AI095692 / AI / NIAID NIH HHS / United States |
Related Institute:
MRI Research Institute (MRIRI)