College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
Vet Microbiol. 2021 Jun;257:109068. doi: 10.1016/j.vetmic.2021.109068. Epub 2021 Apr 10.
Porcine deltacoronavirus (PDCoV) is a swine enteropathogenic coronavirus (CoV) that continues to spread globally, placing strain on economic and public health. Currently, the pathogenic mechanism of PDCoV remains largely unclear, and effective strategies to prevent or treat PDCoV infection are still limited. In this study, the interaction between autophagy and PDCoV replication in LLC-PK1 cells was investigated. We demonstrated that PDCoV infection induced a complete autophagy process. Pharmacologically induced autophagy with rapamycin increased the expression of PDCoV N, while pharmacologically inhibited autophagy with wortmannin decreased the expression of PDCoV N, suggesting that PDCoV-induced autophagy facilitates virus replication. Further experiments showed that PDCoV infection activated p38 signaling pathway to trigger autophagy. Besides, ergosterol peroxide (EP) alleviated PDCoV-induced activation of p38 to suppress autophagy, thus exerting its antiviral effects. Finally, we employed a piglet model of PDCoV infection to demonstrate that EP prevented PDCoV infection by suppressing PDCoV-induced autophagy via p38 signaling pathway in vivo. Collectively, these findings accelerate the understanding of the pathogenesis of PDCoV infection and provide new insights for the development of EP as an effective therapeutic strategy for PDCoV.
猪德尔塔冠状病毒（PDCoV）是一种猪肠道致病性冠状病毒（CoV），持续在全球范围内传播，给经济和公共卫生带来压力。目前，PDCoV 的发病机制在很大程度上仍不清楚，预防或治疗 PDCoV 感染的有效策略仍然有限。在本研究中，研究了自噬与 PDCoV 在 LLC-PK1 细胞中的复制之间的相互作用。我们证明 PDCoV 感染诱导了完整的自噬过程。用雷帕霉素诱导自噬会增加 PDCoV N 的表达，而用渥曼青霉素抑制自噬会降低 PDCoV N 的表达，这表明 PDCoV 诱导的自噬促进了病毒的复制。进一步的实验表明，PDCoV 感染激活了 p38 信号通路，引发自噬。此外，麦角甾醇过氧化物（EP）减轻 PDCoV 诱导的 p38 激活，从而抑制自噬，发挥其抗病毒作用。最后，我们采用 PDCoV 感染仔猪模型，证明 EP 通过抑制 PDCoV 诱导的自噬来预防 PDCoV 感染，该作用是通过 p38 信号通路在体内发挥的。总之，这些发现加速了对 PDCoV 感染发病机制的理解，并为开发 EP 作为 PDCoV 的有效治疗策略提供了新的思路。
