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

Journal of Virology
Mei XuePinghuang Liu

Abstract

Coronavirus replication is closely associated with the endoplasmic reticulum (ER), the primary cellular organelle for protein synthesis, folding, and modification. ER stress is a common consequence in coronavirus-infected cells. However, how the virus-induced ER stress influences coronavirus replication and pathogenesis remains controversial. Here, we demonstrated that infection with the alphacoronavirus transmissible gastroenteritis virus (TGEV) induced ER stress and triggered the unfolded protein response (UPR) in vitro and in vivo, and ER stress negatively regulated TGEV replication in vitro Although TGEV infection activated all three UPR pathways (activating transcription factor 6 [ATF6], inositol-requiring enzyme 1 [IRE1], and protein kinase R-like ER kinase [PERK]), the virus-triggered UPR suppressed TGEV replication in both swine testicular (ST) and IPEC-J2 cells primarily through activation of the PERK-eukaryotic initiation factor 2α (eIF2α) axis, as shown by functional studies with overexpression, small interfering RNA (siRNA), or specific chemical inhibitors. Moreover, we demonstrated that PERK-eIF2α axis-mediated inhibition of TGEV replication occurs through phosphorylated eIF2α-induced overall attenuation of protein...Continue Reading

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Citations

Jul 26, 2019·Journal of Virology·Jaeyeun LeeRichard F Ambinder
Oct 6, 2020·Journal of Veterinary Science·Xiuli LiangWenju Zhang
Jun 7, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shichong HanHuichen Guo
Nov 5, 2019·Frontiers in Cellular and Infection Microbiology·Aracelly Gaete-ArgelFernando Valiente-Echeverría
Sep 10, 2020·Viruses·Nina EiermannAlessia Ruggieri
Jun 22, 2019·Annual Review of Microbiology·To Sing Fung, Ding Xiang Liu
Dec 29, 2020·Frontiers in Pharmacology·José Miguel Vela
May 8, 2021·Frontiers in Pharmacology·Vikas P SukhatmeVidula V Sukhatme
Jan 26, 2021·Annual Review of Microbiology·To Sing Fung, Ding Xiang Liu

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