{"doi":"10.1101/2025.03.04.641538","title":"Poxvirus attack of anti-viral defense pathways unleashes an effector-triggered NF-κB response","abstract":"Abstract Effector-triggered immunity (ETI) is a form of pathogen sensing that involves detection of pathogen-encoded virulence factors or “effectors”. To discover novel ETI pathways in mammals, we developed a screening approach in which individual virulence factors are expressed in human monocytes and transcriptional responses are assessed by RNA-seq. Using this approach, we identify a poxvirus effector, myxoma virus M3.1, which elicits an anti-viral NF-κB response. We find that NF-κB is unleashed by an ETI pathway that senses M3.1 attack of two anti-viral complexes: ZAP and TBK1. NF-κΒ activation occurs because the proteins inhibited by M3.1— N4BP1, ZC3H12A, and TBK1—are negative regulators of NF-κB. Our results illustrate how negative regulators can function as pathogen sensors and establish a systematic approach for the discovery of ETI pathways.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":562903,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1465767,"name":"Joshua Q. Mao","orcid":"0009-0007-5606-8062","position":1,"is_corresponding":false},{"id":248002,"name":"Andrew G. Manford","orcid":"0000-0003-4472-9509","position":2,"is_corresponding":false},{"id":998115,"name":"Ami D. Gutierrez-Jensen","orcid":"0009-0002-5120-6845","position":3,"is_corresponding":false},{"id":6926,"name":"Allon Wagner","orcid":"0000-0001-5095-6009","position":4,"is_corresponding":false},{"id":248007,"name":"Michael Rapé","orcid":"0000-0003-4849-6343","position":5,"is_corresponding":false},{"id":388303,"name":"Grant McFadden","orcid":"0000-0002-2556-3526","position":6,"is_corresponding":false},{"id":1465303,"name":"Masmudur M. Rahman","orcid":"0000-0003-0863-5396","position":7,"is_corresponding":false},{"id":556933,"name":"Moritz M. Gaidt","orcid":"0000-0002-8009-294X","position":8,"is_corresponding":false},{"id":251793,"name":"Russell E. Vance","orcid":"0000-0002-6686-3912","position":9,"is_corresponding":false},{"id":665238,"name":"Brenna C. Remick","orcid":"0000-0001-5333-6657","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T02:56:09.638214Z","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":[]}