{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:08:24Z","timestamp":1790615304477,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T00:00:00Z","timestamp":1661731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Center for Child Health and Development","award":["27-18"],"award-info":[{"award-number":["27-18"]}]},{"name":"National Center for Child Health and Development","award":["2021B-21"],"award-info":[{"award-number":["2021B-21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The type I interferon (IFN) response is one of the primary defense systems against various pathogens. Although rubella virus (RuV) infection is known to cause dysfunction of various organs and systems, including the central nervous system, little is known about how human neural cells evoke protective immunity against RuV infection, leading to controlling RuV replication. Using cultured human neural cells experimentally infected with RuV RA27\/3 strain, we characterized the type I IFN immune response against the virus. RuV infected cultured human neural cell lines and induced IFN-\u03b2 production, leading to the activation of signal transducer and activator of transcription 1 (STAT1) and the increased expression of IFN-stimulated genes (ISGs). Melanoma-differentiation-associated gene 5 (MDA5), one of the cytoplasmic retinoic acid-inducible gene I (RIG-I)-like receptors, is required for the RuV-triggered IFN-\u03b2 mRNA induction in U373MG cells. We also showed that upregulation of RuV-triggered ISGs was attenuated by blocking IFN-\u03b1\/\u03b2 receptor subunit 2 (IFNAR2) using an IFNAR2-specific neutralizing antibody or by repressing mitochondrial antiviral signaling protein (MAVS) expression using MAVS-targeting short hairpin RNA (shRNA). Furthermore, treating RuV-infected cells with BX-795, a TANK-binding kinase 1 (TBK1)\/I kappa B kinase \u03b5 (IKK\u03b5) inhibitor, robustly reduced STAT1 phosphorylation and expression of ISGs, enhancing viral gene expression and infectious virion production. Overall, our findings suggest that the RuV-triggered type I IFN-mediated antiviral response is essential in controlling RuV gene expression and viral replication in human neural cells.<\/jats:p>","DOI":"10.3390\/ijms23179799","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T21:01:31Z","timestamp":1661806891000},"page":"9799","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Rubella Virus Triggers Type I Interferon Antiviral Response in Cultured Human Neural Cells: Involvement in the Control of Viral Gene Expression and Infectious Progeny Production"],"prefix":"10.3390","volume":"23","author":[{"given":"Sayuri","family":"Sakuragi","sequence":"first","affiliation":[{"name":"Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanan","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kodai","family":"Yajima","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan"},{"name":"Department of Life Sciences, School of Agriculture, Meiji University, Kanagawa 214-8571, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeyoshi","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/ni1087","article-title":"The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses","volume":"5","author":"Yoneyama","year":"2004","journal-title":"Nat. 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