title: Porcine epidemic diarrhea virus N protein prolongs S-phase cell cycle, induces endoplasmic reticulum stress, and up-regulates interleukin-8 expression.
abstract: Porcine epidemic diarrhea (PED) is an acute and highly contagious enteric disease of swine caused by porcine epidemic diarrhea virus (PEDV). The porcine intestinal epithelial cell is the PEDV target cell. In this study, we established a porcine intestinal epithelial cell (IEC) line which can stably express PEDV N protein. We also investigate the subcellular localization and function of PEDV N protein by examining its effects on cell growth, cycle progression, interleukin-8 (IL-8) expression, and survival. The results show that the PEDV N protein localizes in the endoplasmic reticulum (ER), inhibits the IEC growth and prolongs S-phase cell cycle. The S-phase is prolonged which is associated with a decrease of cyclin A transcription level and an increase of cyclin A degradation. The IEC expressing PEDV N protein can express higher levels of IL-8 than control cells. Further studies show that PEDV N protein induces ER stress and activates NF-κB, which is responsible for the up-regulation of IL-8 and Bcl-2 expression. This is the first report to demonstrate that PEDV N protein can induce cell cycle prolongation at the S-phase, ER stress and up-regulation interleukin-8 expression. These findings provide novel information on the function of the PEDV N protein and are likely to be very useful in understanding the molecular mechanisms responsible for PEDV pathogenesis.
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Xingang
authors.initials: X
authors.lastname: Xu
authors.forename: Honglei
authors.initials: H
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Jie
authors.initials: J
authors.lastname: Dong
authors.forename: Yabing
authors.initials: Y
authors.lastname: Liang
authors.forename: Hung-Jen
authors.initials: HJ
authors.lastname: Liu
authors.forename: Dewen
authors.initials: D
authors.lastname: Tong
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D016209:Interleukin-8 / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics; D019590:Nucleocapsid Proteins / Q000235:genetics / Q000494:pharmacology*; D053485:Porcine epidemic diarrhea virus / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects*; D013552:Swine; D015854:Up-Regulation
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D019590:Nucleocapsid Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins
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