Vaccinia E5 is a major inhibitor of the DNA sensor cGAS
Yang, N.; Wang, Y.; Dai, P.; Li, T.; Zierhut, C.; Tan, A.; Zhang, T.; Pan, H.; Li, Z.; Ordureau, A.; Xiang, J. Z.; Hendrickson, R. C.; Funabiki, H.; Chen, Z.; Deng, L.
Show 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 largely unknown. In this study, we screened 82 vaccinia viral 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 that elicits proteasome-dependent cGAS degradation. E5 localizes to the cytoplasm and nuclei of infected cells. Cytosolic E5 triggers K48-linked ubiquitination of cGAS and proteasome-dependent degradation via interacting with cGAS. E5 itself also undergoes ubiquitination and degradation. 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, thereby improving the immunogenicity of the viral vector.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- MHC class Ia molecules facilitate MCK2-dependent MCMV infection of macrophages and virus dissemination to the salivary gland 97%
- Murine cytomegalovirus downregulates ERAAP and induces an unconventional T cell response to self 96%
- Systematic analysis of SARS-CoV-2 infection of an ACE2-negative human airway cell 96%
Similar papers in this journal
- The ER membrane protein complex is required to ensure correct topology and stable expression of flavivirus polyproteins 96%
- ACE2 is the critical in vivo receptor for SARS-CoV-2 in a novel COVID-19 mouse model with TNF- and IFNγ-driven immunopathology 96%
- The Relative Binding Position of Nck and Grb2 Adaptors Dramatically Impacts Actin-Based Motility of Vaccinia Virus 96%
Similar papers in this journal
- TRIM25 and ZAP target the Ebola virus ribonucleoprotein complex to mediate interferon-induced restriction 96%
- Vaccinia virus D10 has broad decapping activity that is regulated by mRNA splicing 95%
- ACE2-lentiviral transduction enables mouse SARS-CoV-2 infection and mapping of receptor interactions 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.