The role of endoplasmic reticulum (ER) stress in Japanese encephalitis is largely unknown. In this study, we found that Japanese encephalitis virus (JEV) strain SA14-14-2 regulates the expression of glucose-regulated protein 78 (GRP78), transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), and splicing of X-box-binding protein 1 (XBP1) mRNA in BHK-21 cells. SA14-14-2-induced cytopathic effect and decrease in viability were also observed. Moreover, the inositol-requiring enzyme 1 (IRE1) inhibitor 3,5-dibromosalicylaldehyde and JNK inhibitor SP600125 increased cell viability and reduced cell apoptosis but did not alter virus replication in SA14-14-2-infected BHK-21 cells. These results, for the first time, demonstrate that JEV induces apoptosis by the IRE1/JNK pathway of ER stress response.

中文翻译：

---

日本脑炎病毒通过IRE1 / JNK途径诱导BHK-21细胞内质网应激反应的凋亡。

内质网应激在日本脑炎中的作用尚不清楚。在这项研究中，我们发现日本脑炎病毒（JEV）株SA14-14-2调节葡萄糖调节蛋白78（GRP78），转录因子4（ATF4）和C / EBP同源蛋白（CHOP）的表达，并进行剪接X-box结合蛋白1（XBP1）mRNA在BHK-21细胞中的表达 还观察到SA14-14-2-诱导的细胞病变作用和生存力降低。此外，需要肌醇的酶1（IRE1）抑制剂3,5-二溴水杨醛和JNK抑制剂SP600125增加了细胞活力，减少了细胞凋亡，但没有改变SA14-14-2感染的BHK-21细胞中的病毒复制。这些结果首次证明，JEV通过ER应激反应的IRE1 / JNK途径诱导细胞凋亡。