{"doi":"10.1155/2015/738547","title":"Respiratory Syncytial Virus Nonstructural Proteins Upregulate SOCS1 and SOCS3 in the Different Manner from Endogenous IFN Signaling","abstract":"<jats:p>Respiratory syncytial virus (RSV) infection upregulates genes of the suppressor of cytokine signaling (SOCS) family, which utilize a feedback loop to inhibit type I interferon dependent antiviral signaling pathway. Here, we reconstituted RSV nonstructural (NS) protein expression plasmids (pNS1, pNS2, and pNS1/2) and tested whether NS1 or NS2 would trigger SOCS1 and SOCS3 protein expression. These NS proteins inhibited interferon- (IFN-)<jats:italic>α</jats:italic>signaling through a mechanism involving the induction of SOCS1 and SOCS3, which appeared to be different from autocrine IFN dependent. NS1 induced both SOCS1 and SOCS3 upregulation, while NS2 only induced SOCS1 expression. The induced expression of SOCS1 and SOCS3 preceded endogenous IFN-signaling activation and inhibited the IFN-inducible antiviral response as well as chemokine induction. Treatments with INF-<jats:italic>α</jats:italic>and NS proteins both induced SOCS1 expression; however, they had opposing effects on IFN-<jats:italic>α</jats:italic>-dependent antiviral gene expression. Our results indicate that NS1 and NS2, which induce the expression of SOCS1 or SOCS3, might represent an independent pathway of stimulating endogenous IFN signaling.</jats:p>","journal":"Journal of Immunology Research","year":2015,"id":656455,"datarank":0.5897738449086489,"base_score":3.9318256327243257,"endowment":3.9318256327243257,"self_citation_contribution":0.5897738449086489,"citation_network_contribution":0.0,"self_endowment_contribution":0.5897738449086489,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":50,"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":419859,"name":"Pu Yang","orcid":"0000-0002-8982-0915","position":1,"is_corresponding":false},{"id":693627,"name":"Yan Tang","orcid":"0000-0002-9969-7797","position":2,"is_corresponding":false},{"id":1713614,"name":"Zishu Pan","orcid":null,"position":3,"is_corresponding":false},{"id":1670449,"name":"Dongchi Zhao","orcid":"0000-0002-9454-6041","position":4,"is_corresponding":false},{"id":1713613,"name":"Junwen Zheng","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Respiratory Syncytial Virus Nonstructural Proteins Upregulate SOCS1 and SOCS3 in the Different Manner from Endogenous IFN Signaling","abstract":"<jats:p>Respiratory syncytial virus (RSV) infection upregulates genes of the suppressor of cytokine signaling (SOCS) family, which utilize a feedback loop to inhibit type I interferon dependent antiviral signaling pathway. Here, we reconstituted RSV nonstructural (NS) protein expression plasmids (pNS1, pNS2, and pNS1/2) and tested whether NS1 or NS2 would trigger SOCS1 and SOCS3 protein expression. These NS proteins inhibited interferon- (IFN-)<jats:italic>α</jats:italic>signaling through a mechanism involving the induction of SOCS1 and SOCS3, which appeared to be different from autocrine IFN dependent. NS1 induced both SOCS1 and SOCS3 upregulation, while NS2 only induced SOCS1 expression. The induced expression of SOCS1 and SOCS3 preceded endogenous IFN-signaling activation and inhibited the IFN-inducible antiviral response as well as chemokine induction. Treatments with INF-<jats:italic>α</jats:italic>and NS proteins both induced SOCS1 expression; however, they had opposing effects on IFN-<jats:italic>α</jats:italic>-dependent antiviral gene expression. Our results indicate that NS1 and NS2, which induce the expression of SOCS1 or SOCS3, might represent an independent pathway of stimulating endogenous IFN signaling.</jats:p>","is_dataset_classified":null,"base_score":3.9318256327243257,"endowment":3.9318256327243257,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26557722","pmcid":"PMC4628668","openalex_id":"https://openalex.org/W2156092073","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"81170005","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"30973220","title":null}],"total_grants":2,"fwci":1.766,"citation_percentile":0.84579912,"influential_citations":0,"citation_trend":[{"year":2015,"count":1},{"year":2016,"count":4},{"year":2017,"count":3},{"year":2018,"count":6},{"year":2019,"count":4},{"year":2020,"count":3},{"year":2021,"count":8},{"year":2022,"count":6},{"year":2023,"count":7},{"year":2024,"count":2},{"year":2025,"count":3},{"year":2026,"count":3}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://downloads.hindawi.com/journals/jir/2015/738547.pdf","host_type":"journal"},{"url":"https://downloads.hindawi.com/journals/jir/2015/738547.pdf","host_type":"publisher"},{"url":"http://downloads.hindawi.com/journals/jir/2015/738547.pdf","host_type":"publisher"},{"url":"http://downloads.hindawi.com/journals/jir/2015/738547.xml","host_type":"publisher"},{"url":"https://doi.org/10.1155/2015/738547","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26557722","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4628668","host_type":"repository"},{"url":"https://doaj.org/article/d7bd23d2efd54245a037eb297ecce016","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4628668","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4628668?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["interferon and immune responses","Respiratory viral infections research","Viral Infections and Vectors"],"mesh_terms":["Suppressor of Cytokine Signaling 1 Protein","Suppressor of Cytokine Signaling 3 Protein","Gene Expression Regulation","Humans","Interferons","Phosphorylation","Recombinant Fusion Proteins","2',5'-Oligoadenylate Synthetase","Signal Transduction","Cytokines","Viral Nonstructural Proteins","Respiratory Syncytial Virus, Human","Inflammation Mediators","Cell Line, Tumor","STAT Transcription Factors","Suppressor of Cytokine Signaling Proteins","Myxovirus Resistance Proteins"],"keywords":["SOCS3","Downregulation and upregulation","Endogeny","Suppressor of cytokine signaling 1","Virology","Signal transduction","Immunology","Biology","Cell biology","STAT3","Biochemistry","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-11T20:57:33.839046Z","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":[]}