{"doi":"10.1101/2020.02.13.936252","title":"STAT1-dependent tolerance of intestinal viral infection","abstract":"Abstract Recent evidence indicates that viral components of the microbiota can contribute to intestinal homeostasis and protection from local inflammatory or infectious insults. However, host-derived mechanisms that maintain tolerance to the virome remain largely unknown. Here, we use colonization with the model commensal murine norovirus (MNV CR6) to interrogate host-directed mechanisms of viral tolerance, and show that STAT1 is a central coordinator of tolerance following CR6 colonization. STAT1 restricts CR6 replication to the intestinal tract, prevents systemic viral-induced tissue damage and disease, and regulates antiviral CD4 + and CD8 + T cell responses. In contrast to systemic viral pathogens that drive T cell mediated immunopathology in STAT1-deficient mice, our data indicates that loss of CD4 + or CD8 + T cells and their associated effector functions has no effect on CR6-induced disease. However, therapeutic administration of an antiviral compound to limit viral replication prevented viral-induced tissue damage and death despite ongoing dysregulated antiviral T cell responses. Collectively, our data uncouple the requirement for STAT1-mediated regulation of antiviral T cell responses from innate immune-mediated restriction of viral replication that is necessary for intestinal viral tolerance.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":123453,"datarank":0.27048370495900376,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.06253955079102011,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.06253955079102011,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":3,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.949,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":566328,"name":"Andrew J Sharon","orcid":"0000-0002-0460-5424","position":1,"is_corresponding":false},{"id":566329,"name":"Nicolette M. Fonseca","orcid":"0000-0001-8529-4703","position":2,"is_corresponding":false},{"id":566330,"name":"Rachel L. Simister","orcid":"0000-0002-9807-8652","position":3,"is_corresponding":false},{"id":566787,"name":"Wallace Yuen","orcid":null,"position":4,"is_corresponding":false},{"id":566331,"name":"Blair K Hardman","orcid":"0000-0002-2432-841X","position":5,"is_corresponding":false},{"id":566788,"name":"Hannah G Robinson","orcid":null,"position":6,"is_corresponding":false},{"id":566789,"name":"Jung Hee Seo","orcid":null,"position":7,"is_corresponding":false},{"id":218431,"name":"Joana Rocha‐Pereira","orcid":"0000-0001-8299-3787","position":8,"is_corresponding":false},{"id":14203,"name":"Ian Welch","orcid":null,"position":9,"is_corresponding":false},{"id":218441,"name":"Johan Neyts","orcid":"0000-0002-0033-7514","position":10,"is_corresponding":false},{"id":566332,"name":"Sean A. Crowe","orcid":"0000-0001-8071-2144","position":11,"is_corresponding":false},{"id":566333,"name":"Lisa C. Osborne","orcid":"0000-0002-7170-3235","position":12,"is_corresponding":false},{"id":566786,"name":"Heather A Filyk","orcid":null,"position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:14:59.547352Z","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":[]}