Porcine epidemic diarrhea virus infection induces endoplasmic reticulum stress and unfolded protein response in jejunal epithelial cells of weaned pigs. Issue 1 (January 2022)

• Record Type: Journal Article
• Authors: Chen, Ya-Mei; Gabler, Nicholas K.; Burrough, Eric R.
• Is Part Of: Veterinary pathology. Volume 59:Issue 1(2022)
• Page Start: 82
• Page End: 90
• Publication Date: 2022-01
• Subjects: apoptosis -- caspase-3 -- enteric coronavirus -- endoplasmic reticulum stress -- porcine epidemic diarrhea virus -- unfolded protein response -- pigs; Veterinary pathology -- Periodicals; Pathology, Veterinary -- Periodicals; 636.089607
• DOI: 10.1177/03009858211048622
• Languages: English
• ISSNs: 0300-9858

Abstract

Porcine epidemic diarrhea virus (PEDV) infection leads to diarrhea and subsequently to decreased feed efficiency and growth in weaned pigs. Given that few studies have addressed the host-virus interaction in vivo, this study focused on endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in jejunal epithelial cells during PEDV infection. Eight-week-old pigs ( n = 64) were orally inoculated with PEDV IN19338 strain ( n = 40) or sham-inoculated ( n = 24) and analyzed for PEDV viral RNA shedding using reverse transcription–quantitative polymerase chain reaction and for viral antigen within enterocytes using immunohistochemistry (IHC). ER stress was analyzed in a subset of 9 PEDV-inoculated pigs with diarrhea, detectable viral RNA, and viral antigen (PEDV-immunopositive pigs). Compared with control pigs, PEDV-immunopositive pigs had a reduced ratio of villus height to crypt depth in the jejunum ( P = .002, n = 9 per group), consistent with intestinal injury. The protein levels of ATF6, IRE1, PERK, XBP1u, ATF4, GRP78, and caspase-3 were assessed in jejunal epithelial cells at the villus tips via IHC. Both ER stress and UPR were demonstrated in PEDV-immunopositive pigs by the increased expression of ATF6 ( P = .047), IRE1 ( P = .007), and ATF4 ( P = .001). The expression of GRP78 ( P = .024) and caspase-3 ( P = .004) were also increased, indicating an accompanying increase in ER protein folding capacity and apoptosis. Overall, these results reveal that PEDV infection induces ER stress and UPR in intestinal epithelial cells of weaned pigs.