牛病毒性腹泻病毒感染诱导线粒体自噬功能缺陷调控胃肠道炎症反应机制的研究

牛病毒性腹泻病毒BVDV感染牛羊等动物后引起高热、腹泻、白细胞减少等临床症状，尤其造成幼畜严重腹泻和粘膜病，病死率高达100%，严重影响畜牧业健康和可持续性发展；然而BVDV感染引起幼畜腹泻炎症病变的机制尚未见报道，亟待研究探索。大量研究报道证实腹泻炎症病变与胃肠道运动起博细胞-Cajal间质细胞（ICC）改变之间存在密切关系。前期研究发现，BVDV新疆流行株TC感染造成ICC细胞数量减少和形态发生变化；此外发现ROS水平升高，线粒体膜通透性增加，IL-1和IL-18分泌水平上调，提示线粒体呼吸功能发生异常及ICC细胞发生炎症反应，然而其分子机制尚未明确。所以本项目基于前期研究发现，以BVDV感染诱导ICC细胞改变、线粒体自噬功能变化及ICC细胞炎症反应三者为研究对象，深入探索三者关系及其相互调控分子机制，为阐明BVDV感染导致腹泻炎症病变机理提供理论依据，也为防控BVD提供新靶点。

Bovine viral diarrhea virus （BVDV）infection caused high fever, diarrhea, neutropenia and other clinical symptoms in cattle and other animals, especially infection of neonate caused severe diarrhea and mucosal disease, the mortality rate is up to 100%, which seriously affect the healthy and sustainable development of animal husbandry. However, the mechanisms of BVDV infection cause diarrhea inflammation of neonate have not been reported, and it needs research and exploration. A large number of studies have confirmed that there is a close relationship between the changes of interstitial cells of Cajal (ICC) and inflammatory diseases of diarrhea. Our previous studies found that numerous ICC cells occur morphological change and decreased in number causing by BVDV Xinjiang epidemic strain TC infection. We also found elevating of ROS, increasing of mitochondrial membrane permeability, and increasing of IL-1 and IL-18 secretion, suggesting that mitochondrial respiratory dysfunction and ICC cell inflammation. But its molecular mechanism is not yet clear. Basing on the previous study, this project takes BVDV infection induced ICC cells changes, mitophagy dysfunction and ICC cell inflammatory reaction as research objects, and explores the relationship between three parties and their molecular mechanisms. The results will provide theoretical basis for elucidating the mechanism of BVDV infection leading to inflammatory lesions of diarrhea, and also provide a new target for the prevention and control of BVD.