GRP78 interacts with the Nsp3 of porcine deltacoronavirus and inhibits viral replication.

Abstract

Porcine deltacoronavirus (PDCoV) is an important intestinal coronavirus, which has caused large economic losses to the global pig industry. Endoplasmic reticulum chaperone protein (GRP78) is involved in viral infection replication and regulates the homeostasis of host cells during pathogen infection. However, the role of GRP78 in PDCoV replication remains unclear. In this study, overexpression or knockdown of GRP78 was used to explore effects on PDCoV replication. The interaction between GRP78 and viral non-structural proteins was determined with co-IP and laser confocal microscopy experiments, and the role of GRP78 in PDCoV replication was further determined. GRP78 overexpression significantly inhibited PDCoV replication. PDCoV infection in LLC-PK1 cells decreased the expression of endogenous GRP78, thus demonstrating an antagonistic effect between them. Co-IP and laser confocal microscopy indicated that GRP78 interacted with PDCoV non-structural protein Nsp3, and GRP78 and Nsp3 antagonized each other, thus activating the unfolded protein response (UPR) and the cellular lysosomal autophagy pathway, and inhibiting PDCoV replication in host cells. These results demonstrate a novel mechanism through which the host protein GRP78 regulates viral replication, thus providing new information for understanding the interaction between PDCoV and the host.