{"doi":"10.1101/2022.09.21.508960","title":"Host specific sensing of coronaviruses and picornaviruses by the CARD8 inflammasome","abstract":"Abstract Hosts have evolved diverse strategies to respond to microbial infections, including the detection of pathogen-encoded proteases by inflammasome-forming sensors such as NLRP1 and CARD8. Here, we find that the 3CL protease (3CL pro ) encoded by diverse coronaviruses, including SARS-CoV-2, cleaves a rapidly evolving region of human CARD8 and activates a robust inflammasome response. CARD8 is required for cell death and the release of pro-inflammatory cytokines during SARS-CoV-2 infection. We further find that natural variation alters CARD8 sensing of 3CL pro , including 3CL pro -mediated antagonism rather than activation of megabat CARD8. Likewise, we find that a single nucleotide polymorphism (SNP) in humans reduces CARD8’s ability to sense coronavirus 3CL pros , and instead enables sensing of 3C proteases (3C pro ) from select picornaviruses. Our findings demonstrate that CARD8 is a broad sensor of viral protease activities and suggests that CARD8 diversity contributes to inter- and intra-species variation in inflammasome-mediated viral sensing and immunopathology.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":297566,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"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":0.9542,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":555506,"name":"Rimjhim Agarwal","orcid":"0000-0002-6939-5077","position":1,"is_corresponding":false},{"id":229071,"name":"Nandan S. Gokhale","orcid":"0000-0002-4459-4053","position":2,"is_corresponding":false},{"id":227949,"name":"Jessie Kulsuptrakul","orcid":"0000-0003-3881-4686","position":3,"is_corresponding":false},{"id":555505,"name":"Andrew P. Ryan","orcid":"0000-0002-2630-9837","position":4,"is_corresponding":false},{"id":463485,"name":"Lennice K. Castro","orcid":"0000-0001-6115-6883","position":5,"is_corresponding":false},{"id":555504,"name":"Christopher Beierschmitt","orcid":"0000-0003-0151-1091","position":6,"is_corresponding":false},{"id":281508,"name":"Elizabeth A Turcotte","orcid":"0000-0002-0165-7173","position":7,"is_corresponding":false},{"id":497569,"name":"Elizabeth J. Fay","orcid":"0000-0003-1712-757X","position":8,"is_corresponding":false},{"id":251793,"name":"Russell E. Vance","orcid":"0000-0002-6686-3912","position":9,"is_corresponding":false},{"id":606894,"name":"Jennifer Hyde","orcid":"0000-0001-8062-1672","position":10,"is_corresponding":false},{"id":335067,"name":"Ram Savan","orcid":"0000-0002-3087-1355","position":11,"is_corresponding":false},{"id":281506,"name":"Patrick S. Mitchell","orcid":"0000-0001-8375-9060","position":12,"is_corresponding":false},{"id":555507,"name":"Matthew D. Daugherty","orcid":"0000-0002-4879-9603","position":13,"is_corresponding":false},{"id":555503,"name":"Brian V. Tsu","orcid":"0000-0003-0268-8323","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:31:26.161109Z","pmid":"36172130","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":[]}