{"doi":"10.17615/yq96-sw95","title":"Modulation of type I IFN induction by a virulence determinant within the alphavirus nsP1 protein","abstract":"Alphaviruses are mosquito-borne viruses that cause serious human and animal diseases. Previous studies demonstrated that a determinant within the nsP1/nsP2 cleavage domain of the virulent Sindbis AR86 virus played a key role in regulating adult mouse virulence without adversely affecting viral replication. Additional characterization of this determinant demonstrated that a virus with the attenuating mutation induced more type I IFN production both in vivo and in vitro. Interestingly, this phenotype was not specific to the Sindbis AR86 virus, as a similar mutation in a distantly related alphavirus, Ross River Virus (RRV), also led to enhanced IFN induction. This effect was independent of virus-induced host shutoff, since IRF-3 phosphorylation, which occurs independently of de novo host transcription/translation, was induced more robustly in cells infected with the mutant viruses. Altogether, these results demonstrate that critical determinants within the nsP1/nsP2 cleavage domain play an important role in regulating alphavirus induced IFN responses.","journal":"UNC Libraries","year":2021,"id":230198,"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":0.95,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":601829,"name":"Catherine C. Cruz","orcid":null,"position":1,"is_corresponding":false},{"id":275061,"name":"Mark T. Heise","orcid":"0000-0001-5829-8477","position":2,"is_corresponding":false},{"id":150159,"name":"Robert E. Johnston","orcid":null,"position":3,"is_corresponding":false},{"id":105115,"name":"Stephanie A. Montgomery","orcid":"0000-0001-8012-5302","position":4,"is_corresponding":false},{"id":353045,"name":"Thomas E. Morrison","orcid":"0000-0002-1811-2938","position":5,"is_corresponding":false},{"id":601148,"name":"Jason Simmons","orcid":"0000-0003-1423-306X","position":6,"is_corresponding":false},{"id":601147,"name":"Reed S. Shabman","orcid":"0000-0003-3272-3484","position":7,"is_corresponding":false},{"id":106937,"name":"Mehul S. Suthar","orcid":"0000-0002-2686-8380","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:55:05.844766Z","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":[]}