Because downregulation of each component of the PERK-CHOP-ERO1α-ROS nexus led to reduced viral replication, we propose that PEDV benefits its replication from inducing ER stress and oxidative stress, highlighting UPR as a promising antiviral target for adjunct therapy to combat infections by PEDV and possibly other coronaviruses as well. This evidence concerns the gene DDIT3 and infection.