{"doi":"10.1371/journal.ppat.1007075","title":"Hepatitis C virus NS4B induces the degradation of TRIF to inhibit TLR3-mediated interferon signaling pathway","abstract":null,"journal":"PLOS Pathogens","year":2018,"id":619767,"datarank":0.5775221402565088,"base_score":3.8501476017100584,"endowment":3.8501476017100584,"self_citation_contribution":0.5775221402565088,"citation_network_contribution":0.0,"self_endowment_contribution":0.5775221402565088,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":46,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":236558,"name":"Xuezhi Cao","orcid":"0000-0002-3602-4560","position":1,"is_corresponding":false},{"id":381132,"name":"Qiang Ding","orcid":"0000-0002-6226-869X","position":2,"is_corresponding":false},{"id":832294,"name":"Yanan Zhao","orcid":"0000-0002-6634-2949","position":3,"is_corresponding":false},{"id":1599617,"name":"Zhenliang He","orcid":null,"position":4,"is_corresponding":false},{"id":874755,"name":"Jin Zhong","orcid":"0000-0002-3554-1275","position":5,"is_corresponding":false},{"id":1461346,"name":"Yisha Liang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Hepatitis C virus NS4B induces the degradation of TRIF to inhibit TLR3-mediated interferon signaling pathway","abstract":"Toll-like receptor 3 (TLR3) senses dsRNA intermediates produced during RNA virus replication to activate innate immune signaling pathways through adaptor protein TRIF. Many viruses have evolved strategies to block TLR3-mediated interferon signaling via targeting TRIF. Here we studied how hepatitis C virus (HCV) antagonizes the TLR3-mediated interferon signaling. We found that HCV-encoded NS4B protein inhibited TLR3-mediated interferon signaling by down-regulating TRIF protein level. Mechanism studies indicated that the downregulation of TRIF by NS4B was dependent on caspase8. NS4B transfection or HCV infection can activate caspase8 to promote TRIF degradation, leading to suppression of TLR3-mediated interferon signaling. Knockout of caspase8 can prevent TRIF degradation triggered by NS4B, thereby enhancing the TLR3-mediated interferon signaling activation in response to HCV infection. In conclusion, our work revealed a new mechanism for HCV to evade innate immune response by blocking the TLR3-mediated interferon signaling via NS4B-induced TRIF degradation.","is_dataset_classified":null,"base_score":3.8501476017100584,"endowment":3.8501476017100584,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"29782532","pmcid":"PMC5983870","openalex_id":"https://openalex.org/W2803668583","authors":[],"funders":[{"funder_name":"Chinese National 973 Program","grant_id":"2015CB554300","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"31670172","title":null},{"funder_name":"the Strategic Priority Research Program of the Chinese Academy of Sciences","grant_id":"XDPB03","title":null}],"total_grants":3,"fwci":2.1979,"citation_percentile":0.88096119,"influential_citations":0,"citation_trend":[{"year":2018,"count":1},{"year":2019,"count":5},{"year":2020,"count":7},{"year":2021,"count":13},{"year":2022,"count":6},{"year":2023,"count":9},{"year":2024,"count":1},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1007075&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1007075&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.ppat.1007075","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.ppat.1007075","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/29782532","host_type":"repository"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30444918","host_type":"repository"},{"url":"https://doaj.org/article/ab6c8fac261f42f4800d9ba7b2805642","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC5983870","host_type":"repository"},{"url":"https://figshare.com/articles/dataset/Hepatitis_C_virus_NS4B_induces_the_degradation_of_TRIF_to_inhibit_TLR3-mediated_interferon_signaling_pathway/6296609","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5983870","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6239338","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC5983870","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC5983870?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["interferon and immune responses","Hepatitis C virus research","Immune Response and Inflammation","Adaptor Proteins, Signal Transducing","Adaptor Proteins, Vesicular Transport","CRISPR-Cas Systems","Caspase 8","Caspase 9","Cell Line, Tumor","Gene Knockout Techniques","HEK293 Cells","Hepacivirus","Humans","Immune Evasion","Immunity, Innate","Interferons","Membrane Proteins","Signal Transduction","Toll-Like Receptor 3","Transfection","Viral Nonstructural Proteins","STING Protein"],"mesh_terms":["STING Protein","Humans","Immunity, Innate","Interferons","Membrane Proteins","Transfection","Signal Transduction","Hepacivirus","Viral Nonstructural Proteins","Adaptor Proteins, Vesicular Transport","Cell Line, Tumor","Adaptor Proteins, Signal Transducing","Toll-Like Receptor 3","Caspase 8","Caspase 9","Gene Knockout Techniques","Immune Evasion","HEK293 Cells","CRISPR-Cas Systems"],"keywords":["TRIF","TLR3","Interferon","IRF3","Innate immune system","Signal transduction","Cell biology","Biology","Toll-like receptor","Virology","Immune system","Immunology"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T08:26:57.963677Z","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":[]}