The PERK Arm of the Unfolded Protein Response Negatively Regulates Transmissible Gastroenteritis Virus Replication by Suppressing Protein Translation and Promoting Type I Interferon Production

• DOI: 10.1128/jvi.00431-18
• Publication Date: 2018-05-15T08:18:43Z
• Authors: Mei Xue; Fang Fu; Yanlong Ma; Xin Zhang; Liang Li; Li Feng; Pinghuang Liu
• Keywords: 0301 basic medicine; Swine; Eukaryotic Initiation Factor-2; Transmissible gastroenteritis virus; Immunology; Virus Replication; Microbiology; Activating Transcription Factor 6; Cell Line; 3. Good health; eIF-2 Kinase; 03 medical and health sciences; Protein Biosynthesis; Insect Science; Virology; Interferon Type I; Unfolded Protein Response; Animals

The induction of ER stress is a common outcome in cells infected with coronaviruses. The UPR initiated by ER stress is actively involved in viral replication and modulates the host innate responses to the invading viruses, but these underlying mechanisms remain incompletely understood. We show here that infection with the alphacoronavirus TGEV elicited ER stress in vitro and in vivo , and the UPR PERK-eIF2α branch was predominantly responsible for the suppression of TGEV replication by ER stress. Furthermore, the PERK-eIF2α axis inhibited TGEV replication through direct inhibition of viral proteins due to global translation inhibition and type I IFN induction. These findings highlight a critical role of the UPR PERK-eIF2α pathway in modulating host innate immunity and coronavirus replication.