{"doi":"10.1371/journal.ppat.1011324","title":"Immune evasion strategy involving propionylation by the KSHV interferon regulatory factor 1 (vIRF1)","abstract":"Post-translational modifications (PTMs) are essential for host antiviral immune response and viral immune evasion. Among a set of novel acylations, lysine propionylation (Kpr) has been detected in both histone and non-histone proteins. However, whether protein propionylation occurs in any viral proteins and whether such modifications regulate viral immune evasion remain elusive. Here, we show that Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded viral interferon regulatory factor 1 (vIRF1) can be propionylated in lysine residues, which is required for effective inhibition of IFN-β production and antiviral signaling. Mechanistically, vIRF1 promotes its own propionylation by blocking SIRT6's interaction with ubiquitin-specific peptidase 10 (USP10) leading to its degradation via a ubiquitin-proteasome pathway. Furthermore, vIRF1 propionylation is required for its function to block IRF3-CBP/p300 recruitment and repress the STING DNA sensing pathway. A SIRT6-specific activator, UBCS039, rescues propionylated vIRF1-mediated repression of IFN-β signaling. These results reveal a novel mechanism of viral evasion of innate immunity through propionylation of a viral protein. The findings suggest that enzymes involved in viral propionylation could be potential targets for preventing viral infections.","journal":"PLoS Pathogens","year":2023,"id":335238,"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":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9634,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":378554,"name":"Xuemei Jia","orcid":"0000-0002-9323-4425","position":1,"is_corresponding":false},{"id":1065164,"name":"Yujia He","orcid":null,"position":2,"is_corresponding":false},{"id":1064631,"name":"Xinyue Ma","orcid":"0000-0003-3463-9809","position":3,"is_corresponding":false},{"id":379804,"name":"Xiaoyu Qi","orcid":null,"position":4,"is_corresponding":false},{"id":928876,"name":"Li Wan","orcid":"0000-0001-5675-2429","position":5,"is_corresponding":false},{"id":304016,"name":"Shou‐Jiang Gao","orcid":"0000-0001-6194-1742","position":6,"is_corresponding":false},{"id":407690,"name":"Qin Yan","orcid":"0000-0002-3974-0298","position":7,"is_corresponding":false},{"id":378555,"name":"Chun Lu","orcid":"0000-0002-6078-9352","position":8,"is_corresponding":false},{"id":378549,"name":"Jiale Shi","orcid":"0000-0002-9836-9265","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T01:09:58.338267Z","pmid":"37023208","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":[]}