Porcine epidemic diarrhea virus E protein induces formation of stress granules and attenuates protein translation through activation of the PERK/eIF2α signaling pathway.

Autor: Zheng L; School of Pharmacy, Yancheng Teachers University, Yancheng 224007, PR China; College of Life Sciences, Anqing Normal University, Anqing 246133, PR China., Yang Y; School of Pharmacy, Yancheng Teachers University, Yancheng 224007, PR China., Han Y; School of Pharmacy, Yancheng Teachers University, Yancheng 224007, PR China., Yu J; School of Pharmacy, Yancheng Teachers University, Yancheng 224007, PR China., Wu Z; School of Pharmacy, Yancheng Teachers University, Yancheng 224007, PR China., Kay M; School of Pharmacy, Yancheng Teachers University, Yancheng 224007, PR China., Xia W; College of Marine and Biological Engineering, Yancheng Teachers University, Yancheng 224007, PR China., Chen Z; College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang 524088, PR China., Ma J; College of Life Science and Technology, HeiLongJiang BaYi Agricultural University, Daqing 163319, PR China., Yang X; College of Life Sciences, Anqing Normal University, Anqing 246133, PR China., Yin L; College of Life Sciences, Anqing Normal University, Anqing 246133, PR China., Xu X; School of Pharmacy, Yancheng Teachers University, Yancheng 224007, PR China., Zhang H; School of Pharmacy, Yancheng Teachers University, Yancheng 224007, PR China; Yancheng Engineering Technology Research Center of Antibody Drugs and Immunodetection, Yancheng Teachers University, Yancheng 224007, PR China; Jiangsu Province Engineering Research Center of Tumor Targeted Nano Diagnostic and Therapeutic Materials, Yancheng Teachers University, Yancheng 224007, PR China. Electronic address: zhangh01@yctu.edu.cn.
Jazyk: angličtina
Zdroj: Veterinary microbiology [Vet Microbiol] 2024 Jun; Vol. 293, pp. 110095. Date of Electronic Publication: 2024 Apr 16.
DOI: 10.1016/j.vetmic.2024.110095
Abstrakt: Porcine epidemic diarrhea virus (PEDV) envelope protein (E) has been characterized as an important structural protein that plays critical roles in the interplay with its host to affect the virus life cycle. Stress granules (SGs) are host translationally silent ribonucleoproteins, which are mainly induced by the phosphorylation of eIF2α in the PERK/eIF2α signaling pathway. Our previous study found that PEDV E protein caused endoplasmic reticulum stress response (ERS)-mediated suppression of antiviral proteins' translation. However, the link and the underlying mechanism by which PEDV induces SGs formation and suppresses host translation remain elusive. In this study, our results showed that PEDV E protein significantly elevated the expression of GRP78, CANX, and phosphorylation of PERK and eIF2α, indicating that the PERK/eIF2α branch of ERS was activated. PEDV E protein localized to the ER and aggregated into puncta to reconstruct ER structure, and further induced SGs formation, which has been caused through upregulating the G3BP1 expression level. In addition, a significant global translational stall and endogenous protein translation attenuation were detected in the presence of E protein overexpression, but the global mRNA transcriptional level remained unchanged, suggesting that the shutoff of protein translation was associated with the translation, not with the transcription process. Collectively, this study demonstrates that PERK/eIF2α activation is required for SGs formation and protein translation stall. This study is beneficial for us to better understand the mechanism by which PEDV E suppresses host protein synthesis, and provides us a new insight into the host translation regulation during virus infection.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: