维生素D3缓解仔猪PEDV感染效应及JAK/STAT3信号介导机制研究

猪流行性腹泻是目前危害全球养猪业的主要疾病之一。VD3具有重要的抗病毒免疫调节功能，但能否缓解猪流行性腹泻病毒（PEDV）感染尚不清楚。JAK/STAT3信号通路在干扰素调节抗病毒反应中发挥着重要的负调控作用，其上游负调控因子SOCSs表达又受VD受体调控。然而，有关JAK/STAT3在PEDV感染及VD3抗病毒免疫中的作用尚无报道。因此，本项目拟采用体内外相结合的方法，在通过饲养试验研究VD3缓解仔猪PEDV感染的效应，初步建立JAK/STAT3与PEDV感染和VD3抗感染间关系的基础上，以IPEC-J2细胞为模型，通过基因敲除和过表达、转录组分析等技术手段，解析STAT3在PEDV感染复制中的具体作用；最后，通过染色质免疫共沉淀等技术，探明VD3能否通过调控JAK/STAT3通路缓解PEDV感染，挖掘VD3作用的关键靶点。研究结果将为解析VD3的抗PEDV感染效应和机制提供理论依据。

Porcine epidemic diarrhea is one of the most major diseases, which resulted in devastating economic losses to the swine industry worldwide. Increasing evidence indicates that vitamin D3 (VD3) has an antiviral immunomodulatory function, however, it is not clear whether VD3 can alleviate porcine epidemic diarrhea virus (PEDV) infection in piglets. JAK/STAT3 signaling pathway plays an important negative regulatory role in interferon-mediated antiviral response, and its upstream negative regulator SOCS is regulated by VD receptor. However, the role of JAK/STAT3 in PEDV infection and VD3 antiviral immunity has not been reported. Therefore, the present project is to study the effects and underlying mechanism of VD3 on alleviating PEDV infection in piglets by in vivo and in vitro experiments. Firstly, the piglets feeding trial will be carried out to investigate the alleviating effect of VD3 on PEDV infection. The relationship among JAK/STAT3 pathway, PEDV infection and the antiviral immunity of VD3 will be established preliminarily. Then, the specific function of STAT3 in PEDV infection and replication will be elucidated by using gene knockout and overexpression, transcriptome analysis and other techniques, in IPEC-J2 jejunum cell model. Finally, we aim to investigate whether VD3 can alleviate PEDV infection via regulating the JAK/STAT3 pathway and to explore the key target by using gene knockout technology and chromatin immunoprecipitation. The results of this project will be of great significance for us to illustrate the anti-PEDV infection effect and the underlying mechanism of VD3.