Porcine epidemic diarrhea virus activates PERK-ROS axis to benefit its replication in Vero E6 cells.
Vet Res
; 54(1): 9, 2023 Feb 03.
Article
en En
| MEDLINE
| ID: mdl-36737830
ABSTRACT
Of the three branches of unfolded protein response (UPR) that were reportedly activated by porcine epidemic diarrhea virus (PEDV), PERK is recently shown to act as an upstream regulator of oxidative response of the cells. However, it remains unknown if and how PERK activation during PEDV infection would result in oxidative stress, and whether activation of PERK and its downstream molecules affect PEDV replication. Here, we demonstrate that infection with the PEDV strain YJH/2015 triggered UPR in Vero E6 cells by activating the PERK/eIF2α pathway and led to significant increase in the expression of proapoptotic protein C/EBP homologous protein (CHOP) and ER oxidoreductase 1 alpha (ERO1α). Inhibition of PERK by short hairpin RNA (shRNA) or GSK2606414 and knockdown of CHOP by small interfering RNA reduced expression of ERO1α and generation of ROS in PEDV-infected cells. Inhibition of ERO1α by shRNA or EN460 decreased PEDV-induced ROS generation. Genetic or pharmacological inhibition of each component of PERK, CHOP, ERO1α, and ROS led to significant suppression of PEDV replication. Collectively, our study provides the first evidence that PEDV manipulates endoplasmic reticulum to perturb its redox homeostasis via the PERK-CHOP-ERO1α-ROS axis in favor of its replication.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Virus de la Diarrea Epidémica Porcina
Límite:
Animals
Idioma:
En
Revista:
Vet Res
Asunto de la revista:
MEDICINA VETERINARIA
Año:
2023
Tipo del documento:
Article