Furthermore, α-CoV and β-CoV may induce ER stress in the infected cells [235]. PEDV ORF3, as the only accessory protein encoded by PEDV, is thought to be related to virus production and virulence of PEDV [68]. A series of studies suggest that ORF3 plays multiple roles, in addition to acting as an ion channel during PEDV replication. Recent studies show that PEDV ORF3 consists of four transmembrane domains (TMDs) and localizes in the cytoplasm in the aggregation manner [236]. ORF3 is a transmembrane protein, and the confocal microscopy analysis indicates that the aggregated ORF3 localizes in the ER to induce the ER stress associated with either apoptosis or autophagy. However, PEDV ORF3 induces the autophagy via driving conversion of LC3-I to LC3-II, but not influencing the apoptosis. ORF3-induced autophagy is dependent on ER stress response. PEDV ORF3 triggers ER stress response via the up-regulation of GRP78 protein expression and the activation of the PERK-eIF2α signaling pathway. Moreover, ORF3 protein is identified as an IFN antagonist to block IFN response by an unknown mechanism in PEDV-infected cells [65]. The functions of PEDV ORF3 should be further exploited.