DEV infection induces endoplasmic reticulum stress and activates inflammatory responses in duck intestinal epithelial cells.

Duck enteritis virus (DEV), a member of the Herpesviridae family, causes an acute and highly contagious disease in waterfowl characterized by vascular injury and severe gastrointestinal lesions. Although DEV infection is known to disrupt cellular homeostasis, the interplay between DEV-induced endoplasmic reticulum (ER) stress and host inflammatory responses in intestinal epithelial cells (IECs) remains poorly understood. We developed an in vitro model using DEV infection in primary duck IECs to study the activation of the unfolded protein response (UPR) and its association with downstream immunomodulatory effects. Our results demonstrated that DEV infection significantly altered ER ultrastructure, characterized by severe rough ER dilation, and triggered ER stress as evidenced by the early upregulation of the chaperone GRP78. Mechanistically, DEV infection was associated with the activation of the PERK-eIF2α-ATF4-CHOP and IRE1α-XBP1 axes of the UPR, while the ATF6 branch showed no significant cleavage under our experimental conditions. Furthermore, activation of the PERK branch was associated with sustained upregulation of the NLRP3 inflammasome and the NF-κB signaling pathway, which correlated with the accumulation of pro-inflammatory cytokines IL-1β and IL-6. Concurrently, the IRE1α branch was associated with the phosphorylation of JNK and the expression of TRAF2, further corresponding to the secretion of IL-1 and TNF-α. Notably, Tunicamycin (Tm)-induced ER stress partially mimicked, but did not fully recapitulate, the robust and sustained inflammatory profile induced by viral infection. These findings suggest a strong correlation between DEV-induced UPR activation and the inflammatory milieu of IECs, providing novel insights into the pathogenesis of DEV-induced enteritis and identifying potential targets for antiviral intervention.