Japanese encephalitis virus induces apoptosis by the IRE1/JNK pathway of ER stress response in BHK-21 cells.

Abstract

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.