{"doi":"10.1371/journal.ppat.1012398","title":"Species-specific IL-1β is an inflammatory sensor of Seneca Valley Virus 3C Protease","abstract":"Inflammasomes play pivotal roles in inflammation by processing and promoting the secretion of IL-1β. Caspase-1 is involved in the maturation of IL-1β and IL-18, while human caspase-4 specifically processes IL-18. Recent structural studies of caspase-4 bound to Pro-IL-18 reveal the molecular basis of Pro-IL-18 activation by caspase-4. However, the mechanism of caspase-1 processing of pro-IL-1β and other IL-1β-converting enzymes remains elusive. Here, we observed that swine Pro-IL-1β (sPro-IL-1β) exists as an oligomeric precursor unlike monomeric human Pro-IL-1β (hPro-IL-1β). Interestingly, Seneca Valley Virus (SVV) 3C protease cleaves sPro-IL-1β to produce mature IL-1β, while it cleaves hPro-IL-1β but does not produce mature IL-1β in a specific manner. When the inflammasome is blocked, SVV 3C continues to activate IL-1β through direct cleavage in porcine alveolar macrophages (PAMs). Through molecular modeling and mutagenesis studies, we discovered that the pro-domain of sPro-IL-1β serves as an 'exosite' with its hydrophobic residues docking into a positively charged 3C protease pocket, thereby directing the substrate to the active site. The cleavage of sPro-IL-1β generates a monomeric and active form of IL-1β, initiating the downstream signaling. Thus, these studies provide IL-1β is an inflammatory sensor that directly detects viral protease through an independent pathway operating in parallel with host inflammasomes.","journal":"PLoS Pathogens","year":2024,"id":440803,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":700315,"name":"Zhenchao Zhao","orcid":"0000-0002-3715-4308","position":1,"is_corresponding":false},{"id":1252761,"name":"Cheng Zhu","orcid":"0009-0005-7482-7320","position":2,"is_corresponding":false},{"id":1064204,"name":"Lvye Chai","orcid":null,"position":3,"is_corresponding":false},{"id":1064203,"name":"Yan Ya","orcid":null,"position":4,"is_corresponding":false},{"id":1063716,"name":"Ye Yuan","orcid":"0000-0002-0298-2023","position":5,"is_corresponding":false},{"id":230786,"name":"Lei Wu","orcid":"0000-0003-1875-7880","position":6,"is_corresponding":false},{"id":334997,"name":"Minjie Li","orcid":"0000-0003-0616-4826","position":7,"is_corresponding":false},{"id":1252762,"name":"Xiaohan Jiang","orcid":"0009-0000-8871-3088","position":8,"is_corresponding":false},{"id":1063717,"name":"Haiwei Wang","orcid":"0000-0002-0588-2511","position":9,"is_corresponding":false},{"id":245750,"name":"Zheng Liu","orcid":"0000-0001-6952-3406","position":10,"is_corresponding":false},{"id":264702,"name":"Pingwei Li","orcid":"0000-0002-1815-3107","position":11,"is_corresponding":false},{"id":1063721,"name":"Xin Li","orcid":"0000-0003-1636-8910","position":12,"is_corresponding":false},{"id":37138,"name":"Xiang‐Yu Huang","orcid":"0000-0001-6372-5998","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T02:01:01.842286Z","pmid":"39038050","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":[]}