Opposite Roles of RNase and Kinase Activities of Inositol-Requiring Enzyme 1 (IRE1) on HSV-1 Replication.

ABSTRACT: In response to the endoplasmic reticulum (ER) stress induced by herpes simplex virus type 1 (HSV-1) infection, host cells activate the unfolded protein response (UPR) to reduce the protein-folding burden in the ER. The regulation of UPR upon HSV-1 infection is complex, and the downstream effectors can be detrimental to viral replication. Therefore, HSV-1 copes with the UPR to create a beneficial environment for its replication. UPR has three branches, including protein kinase RNA (PKR)-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activated transcription factor 6 (ATF6). IRE1? is the most conserved branch of UPR which has both RNase and kinase activities. Previous studies have shown that IRE1? RNase activity was inactivated during HSV-1 infection. However, the effect of the two activities of IRE1? on HSV-1 replication remains unknown. Results in this study showed that IRE1? expression was up-regulated during HSV-1 infection. We found that in HEC-1-A cells, increasing RNase activity, or inhibiting kinase activity of IRE1? led to viral suppression, indicating that the kinase activity of IRE1? was beneficial, while the RNase activity was detrimental to viral replication. Further evidence showed that the kinase activity of IRE1? leads to the activation of the JNK (c-Jun N-terminal kinases) pathway, which enhances viral replication. Taken together, our evidence suggests that IRE1? is involved in HSV-1 replication, and its RNase and kinase activities play differential roles during viral infection.

SUBMITTER: Su A 

PROVIDER: S-EPMC5618002 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature