FcRn在猪流行性腹泻病毒感染中的作用及机制研究

近年来研究表明IgG在黏膜抗感染中也发挥重要作用，而FcRn是IgG的唯一转运受体。我们前期研究发现传染性胃肠炎病毒（TGEV）感染猪小肠上皮细胞上调FcRn表达，并阐明了其调控机制。然而我们发现与TGEV同属于α冠状病毒的猪流行性腹泻病毒（PEDV）感染猪小肠上皮细胞下调FcRn表达，其调控机制以及FcRn在PEDV感染中所起的作用尚不清楚。本项目拟分析PEDV感染IPI-2I细胞对FcRn表达的动态变化，解析其调控FcRn表达的信号通路，筛选参与下调FcRn表达的病毒蛋白并确定其关键功能域，采用抗体阻断、干扰或过表达以及FcRn敲除细胞系探讨FcRn对PEDV增殖的影响，探究PEDV与FcRn之间的相互作用，阐明FcRn在PEDV感染中的作用机制。为揭示PEDV的致病机理和宿主抵抗病毒入侵的机制提供新的理论依据。FcRn可能作为抗PEDV感染的靶标，为PED的防控提供新思路。

Recent studies have shown that IgG also plays an important role in mucosal anti-infection, and FcRn is the only receptor for IgG transport. Our research results revealed that FcRn expression was up-regulated in porcine small intestinal epithelial cells infected with infectious gastroenteritis virus (TGEV) and its regulatory mechanism was clarified. However, we found that FcRn expression was down-regulated in porcine small intestinal epithelial cells with infection of porcine epidemic diarrhea virus (PEDV), its regulatory mechanism and the role of FcRn during PEDV infection are unclear. In this study we intend to analyze the dynamic of FcRn expression in IPI-2I cells after infection of PEDV, investigate the signaling pathways of down-regulated FcRn expression caused by PEDV, screen key domains of viral proteins involved in down-regulating FcRn expression, explore the role of FcRn on PEDV proliferation with specific blocking antibody, RNAi-mediated silencing, overexpression or knockout cell lines, and the further exploration of the interaction between PEDV and FcRn to elucidate the mechanism of FcRn involved in PEDV infection. It will provide a theoretical basis for revealing the pathogenesis of PEDV, and the mechanism of host resistance against PEDV invasion. FcRn may be a target against PEDV infection, it will provide new insights for prevention and controlling of PED.