{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:54:37Z","timestamp":1791942877045,"version":"4.3.4"},"reference-count":10,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroimmunomodulation"],"published-print":{"date-parts":[[2022]]},"abstract":"<b><i>Introduction:<\/i><\/b> Invasion of viruses into the brain causes viral encephalitis, which can be fatal and causes permanent brain damage. The blood-brain barrier (BBB) protects the brain by excluding harmful substances and microbes. Brain microvascular endothelial cells are important components of the BBB; however, the mechanisms of antiviral reactions in these cells have not been fully elucidated. Zinc-finger antiviral protein (ZAP) is a molecule that restricts the infection of various viruses, and there are 2 major isoforms: ZAPL and ZAPS. Toll-like receptor 3 (TLR3), a pattern-recognition receptor against viral double-stranded RNA, is implicated in antiviral innate immune reactions. The aim of this study was to investigate the expression of ZAP in cultured hCMEC\/D3 human brain microvascular endothelial cells treated with an authentic TLR3 agonist polyinosinic-polycytidylic acid (poly IC). <b><i>Methods:<\/i><\/b> hCMEC\/D3 cells were cultured and treated with poly IC. Expression of ZAPL and ZAPS mRNA was investigated using quantitative reverse transcription-polymerase chain reaction, and protein expression of these molecules was examined using western blotting. The role of nuclear factor-\u03baB (NF-\u03baB) was examined using the NF-\u03baB inhibitor, SN50. The roles of interferon (IFN)-\u03b2, IFN regulatory factor 3 (IRF3), tripartite motif protein 25 (TRIM25), and retinoic acid-inducible gene-I (RIG-I) in poly IC-induced ZAPS expression were examined using RNA interference. Propagation of Japanese encephalitis virus (JEV) was examined using a focus-forming assay. <b><i>Results:<\/i><\/b> ZAPS mRNA and protein expression was upregulated by poly IC, whereas the change of ZAPL mRNA and protein levels was minimal. Knockdown of IRF3 or TRIM25 decreased the poly IC-induced upregulation of ZAPS, whereas knockdown of IFN-\u03b2 or RIG-I did not affect ZAPS upregulation. SN50 did not affect ZAPS expression. Knockdown of ZAP enhanced JEV propagation. <b><i>Conclusion:<\/i><\/b> ZAPL and ZAPS were expressed in hCMEC\/D3 cells, and ZAPS expression was upregulated by poly IC. IRF3 and TRIM25 are involved in poly IC-induced upregulation of ZAPS. ZAP may contribute to antiviral reactions in brain microvascular endothelial cells and protect the brain from invading viruses such as JEV. <\/jats:p>","DOI":"10.1159\/000521012","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T22:00:29Z","timestamp":1640210429000},"page":"349-358","source":"Crossref","is-referenced-by-count":5,"title":["Expression of Zinc-Finger Antiviral Protein in hCMEC\/D3 Human Cerebral Microvascular Endothelial Cells: Effect of a Toll-Like Receptor 3 Agonist"],"prefix":"10.1159","volume":"29","author":[{"given":"Mako","family":"Okudera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minami","family":"Odawara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Arakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5599-1110","authenticated-orcid":false,"given":"Shogo","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Seya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoh","family":"Matsumiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riko","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangli","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3781-6121","authenticated-orcid":false,"given":"Eiji","family":"Morita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadaatsu","family":"Imaizumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2020.09.011"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1007\/s12028-020-01049-4"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074276"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.1865"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0040021"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1509745112"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2005.01.006"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1186\/2045-8118-10-16"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1159\/000484258"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2019.103678"}],"container-title":["Neuroimmunomodulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/521012","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/521012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:35:38Z","timestamp":1745422538000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000521012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,22]]},"references-count":10,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,12,13]]},"published-print":{"date-parts":[[2022,12,20]]}},"URL":"https:\/\/doi.org\/10.1159\/000521012","archive":["Portico"],"relation":{},"ISSN":["1021-7401","1423-0216"],"issn-type":[{"value":"1021-7401","type":"print"},{"value":"1423-0216","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,22]]}}}