{"doi":"10.1101/2021.10.25.465197","title":"Vaccinia E5 is a major inhibitor of the DNA sensor cGAS","abstract":"SUMMARY 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":215290,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9664,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":810003,"name":"Yi Wang","orcid":"0000-0001-9921-0304","position":1,"is_corresponding":false},{"id":574154,"name":"Peihong Dai","orcid":null,"position":2,"is_corresponding":false},{"id":810004,"name":"Tuo Li","orcid":"0000-0001-6268-7520","position":3,"is_corresponding":false},{"id":240916,"name":"Christian Zierhut","orcid":"0000-0003-3501-603X","position":4,"is_corresponding":false},{"id":810005,"name":"Adrian Y. Tan","orcid":"0000-0001-6969-6606","position":5,"is_corresponding":false},{"id":109215,"name":"Tuo Zhang","orcid":"0000-0001-5396-918X","position":6,"is_corresponding":false},{"id":345821,"name":"Heng Pan","orcid":"0000-0002-5407-5687","position":7,"is_corresponding":false},{"id":618828,"name":"Zhuoning Li","orcid":"0009-0005-9064-8170","position":8,"is_corresponding":false},{"id":242343,"name":"Alban Ordureau","orcid":"0000-0002-4924-8520","position":9,"is_corresponding":false},{"id":109227,"name":"Jenny Xiang","orcid":"0000-0003-0484-2769","position":10,"is_corresponding":false},{"id":409428,"name":"Ronald C. Hendrickson","orcid":"0000-0002-0851-903X","position":11,"is_corresponding":false},{"id":240922,"name":"Hironori Funabiki","orcid":"0000-0003-4831-4087","position":12,"is_corresponding":false},{"id":108354,"name":"Zhijian J. Chen","orcid":"0000-0002-8475-8251","position":13,"is_corresponding":false},{"id":573544,"name":"Liang Deng","orcid":"0000-0002-8467-9342","position":14,"is_corresponding":false},{"id":573542,"name":"Ning Yang","orcid":"0000-0001-5121-7208","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-18T23:52:55.971300Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}