{"doi":"10.12688/wellcomeopenres.17237.1","title":"Innate triggering and antiviral effector functions of Activin A","abstract":"<ns3:p> <ns3:bold>Background:</ns3:bold> First-line defence against viral infection is contingent upon rapid detection of conserved viral structural and genomic motifs by pattern recognition receptors, followed by activation of the type I IFN response and establishment of an antiviral state. Novel antiviral functions of bone morphogenetic protein and related activin cytokines, acting in conjunction with, and independently of, type I IFN, have recently been described. How these antiviral effects are mediated and triggered by viral infection has not been defined. </ns3:p> <ns3:p> <ns3:bold>Methods:</ns3:bold> Microarray and RNAseq data from hepatoma-derived cell lines stimulated with Activin A <ns3:italic>in vitro</ns3:italic> were interrogated both by pathway analysis and for evidence of IFN-stimulated gene induction. Liver tissue obtained from patients with chronic HCV were examined by real-time quantitative polymerase chain reaction (RT-qPCR) for evidence of Activin A induction. Activin expression by peripheral blood mononuclear cells exposed to nucleic acid analogues was quantified by RT-qCR, whereas induction dynamics in acute infection was investigated in <ns3:italic>in vitro</ns3:italic> Sendai virus infection and a murine influenza A. </ns3:p> <ns3:p> <ns3:bold>Results:</ns3:bold> Transcriptomic analyses delineated strikingly congruent patterns of gene regulation in hepatocytes stimulated with recombinant Activin A and IFNα <ns3:italic>in vitro</ns3:italic> . Activin A mRNA, encoded by <ns3:italic>INHBA</ns3:italic> , is induced upon activation of RIG-I, MDA5 and TLR7/8 viral nucleic acid sensors <ns3:italic>in vitro</ns3:italic> , across multiple cell lines and in human peripheral blood mononuclear cells. <ns3:italic>In vivo</ns3:italic> , imurine influenza A also upregulated <ns3:italic>Inhba</ns3:italic> mRNA in the lung; this local upregulation of <ns3:italic>Inhba</ns3:italic> is retained in MAVS knockout mice, indicating roles for non-RIG-I-like receptors in its induction. Activin induction and signalling were also detectable in patients with chronic viral hepatitis. </ns3:p> <ns3:p> <ns3:bold>Conclusions:</ns3:bold> These data suggest Activin A is triggered in parallel with type I IFN responses and can trigger related antiviral effector functions, with implications for the development of targeted antiviral therapies and revealing novel facets of Activin biology. </ns3:p>","journal":"Wellcome Open Research","year":2022,"id":295650,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"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":555618,"name":"Narayan Ramamurthy","orcid":"0000-0002-3297-2483","position":1,"is_corresponding":false},{"id":814113,"name":"Emanuele Marchi","orcid":"0000-0003-1741-9353","position":2,"is_corresponding":false},{"id":981920,"name":"Ruth Eichinger","orcid":null,"position":3,"is_corresponding":false},{"id":191446,"name":"Lian Li","orcid":null,"position":4,"is_corresponding":false},{"id":814704,"name":"Paolo Fabris","orcid":null,"position":5,"is_corresponding":false},{"id":338689,"name":"Hal Drakesmith","orcid":"0000-0002-8503-6103","position":6,"is_corresponding":false},{"id":106117,"name":"Paul Klenerman","orcid":"0000-0003-4307-9161","position":7,"is_corresponding":false},{"id":814112,"name":"Kinda Al-Hourani","orcid":"0000-0002-7730-9001","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T00:31:08.861377Z","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":[]}