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ER stress sensor protein kinase R-like endoplasmic reticulum kinase (PERK) has been reported to induce apoptosis under acute or prolonged ER stress. However, whether the PERK pathway of ER stress response plays important roles in JEV-induced apoptosis and encephalitis remains unknown. Here, we found that JEV infection activates ER stress sensor PERK in neuronal cells and mouse brains. PERK activation induces apoptosis via the PERK-ATF4-CHOP apoptosis pathway upon JEV infection. Among the JEV proteins prM, E, NS1, NS2A, NS2B, and NS4B, only NS4B activates PERK. Moreover, activated PERK participates in apoptosis and encephalitis induced by JEV and NS4B. These findings provide a novel therapeutic approach for JEV-caused encephalitis.<\/jats:p>","DOI":"10.1128\/jvi.00887-19","type":"journal-article","created":{"date-parts":[[2019,6,12]],"date-time":"2019-06-12T12:54:55Z","timestamp":1560344095000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":82,"title":["Japanese Encephalitis Virus Induces Apoptosis and Encephalitis by Activating the PERK Pathway"],"prefix":"10.1128","volume":"93","author":[{"given":"Qianruo","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Pathogenic Microorganism and College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu","family":"Xin","sequence":"additional","affiliation":[{"name":"Institute of Pathogenic Microorganism and College of Bioscience and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, 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