Abstract Introduction Porcine epidemic diarrhoea virus (PEDV) infection causes watery diarrhoea, vomiting, anorexia, and weight loss, especially among neonatal piglets, inflicting on them morbidity and mortality potentially reaching 90%–100%. Despite it being known that certain mammalian cell phases are arrested by PEDV, the mechanisms have not been elucidated, and PEDV pathogenesis is poorly understood. This study determined the effect of an epidemic PEDV strain on cell cycle progression. Material and Methods We observed the effect of the PEDV SHpd/2012 strain on an infected Vero cell cycle through flow cytometry and Western blot, investigating the interrelationships of cell-cycle arrest, the DNA damage–signalling pathway caused by PEDV and the phosphorylation levels of the key molecules Chk.2 and H2A.X involved upstream and downstream in this pathway. Results PEDV induced Vero cell-cycle arrest at the G1/G0 phase. The phosphorylation levels of Chk.2 and H2A.X increased with the prolongation of PEDV infection, and no significant cell-cycle arrest was observed after treatment with ATM or Chk.2 inhibitors. The proliferation of PEDV was also inhibited by treatment with ATM or Chk.2 inhibitors. Conclusion PEDV-induced cell-cycle arrest is associated with activation of DNA damage–signalling pathways. Our findings elucidate the molecular basis of PEDV replication and provide evidence to support further evaluation of PEDV pathogenesis.

中文翻译：

---

猪流行性腹泻病毒通过 DNA 损伤信号通路诱导细胞周期停滞

摘要 简介 猪流行性腹泻病毒（PEDV）感染会导致水样腹泻、呕吐、厌食和体重减轻，尤其是在新生仔猪中，其发病率和死亡率可能达到 90%–100%。尽管已知某些哺乳动物细胞期会被 PEDV 阻止，但其机制尚未阐明，PEDV 的发病机制也知之甚少。本研究确定了流行性 PEDV 毒株对细胞周期进程的影响。材料和方法 我们通过流式细胞术和蛋白质印迹观察了 PEDV SHpd/2012 株对感染的 Vero 细胞周期的影响，研究了细胞周期停滞、PEDV 引起的 DNA 损伤信号通路和磷酸化水平的相互关系。关键分子 Chk.2 和 H2A。X 涉及该途径的上游和下游。结果 PEDV 在 G1/G0 期诱导 Vero 细胞周期停滞。Chk.2和H2A.X的磷酸化水平随着PEDV感染的延长而增加，并且在用ATM或Chk.2抑制剂处理后未观察到明显的细胞周期停滞。PEDV 的增殖也受到 ATM 或 Chk.2 抑制剂治疗的抑制。结论 PEDV 诱导的细胞周期停滞与 DNA 损伤信号通路的激活有关。我们的研究结果阐明了 PEDV 复制的分子基础，并提供了支持进一步评估 PEDV 发病机制的证据。用 ATM 或 Chk.2 抑制剂治疗后未观察到明显的细胞周期停滞。PEDV 的增殖也受到 ATM 或 Chk.2 抑制剂治疗的抑制。结论 PEDV 诱导的细胞周期停滞与 DNA 损伤信号通路的激活有关。我们的研究结果阐明了 PEDV 复制的分子基础，并提供了支持进一步评估 PEDV 发病机制的证据。用 ATM 或 Chk.2 抑制剂治疗后未观察到明显的细胞周期停滞。PEDV 的增殖也受到 ATM 或 Chk.2 抑制剂治疗的抑制。结论 PEDV 诱导的细胞周期停滞与 DNA 损伤信号通路的激活有关。我们的研究结果阐明了 PEDV 复制的分子基础，并提供了支持进一步评估 PEDV 发病机制的证据。