模式识别受体调控IRF1-BST2通路抑制猪流行性腹泻病毒增殖的分子机制研究

猪流行性腹泻病毒（PEDV）是危害养猪业最主要的病原之一。天然免疫反应在宿主抵御病毒感染的过程中发挥着重要的作用。申请者前期研究发现：在PEDV感染的过程中，宿主细胞利用IRF1上调天然免疫限制性因子BST2的表达，进一步激活选择性自噬降解PEDV N蛋白，抑制病毒增殖。宿主细胞识别PEDV并激活IRF1-BST2抑制病毒增殖的分子机制暂不清楚。本项目拟通过染色质免疫共沉淀及荧光素酶等试验筛选参与调控IRF1表达的关键蛋白，利用特异性激动剂及基因编辑等试验分析参与识别病毒并调控IRF1的模式识别受体，解析PEDV感染过程中宿主因子上调IRF1表达的分子机制，阐明模式识别受体介导宿主蛋白激活IRF1的作用机理，揭示模式识别受体识别PEDV并介导相关蛋白上调IRF1-BST2抑制病毒增殖的分子机制。以期增加对宿主利用天然免疫抑制病毒增殖的认识，为科学防控和治疗PED提供理论依据和研究方向。

Porcine epidemic diarrhea virus (PEDV) is one of the most important pathogens in the swine industry, which caused great harm to the world pig industry. The innate immune response plays an important role in the host cell's defense against viral infection. In our previous research, we found that the host cells up-regulated the expression of innate immunity restriction factor BST2 by IRF1, and BST2 degraded PEDV N protein by selective autophagy to inhibit PEDV proliferation. The molecular mechanism of how host cells effectively recognize PEDV and activate IRF1-BST2 to inhibit PEDV proliferation has not been clear. This project will use chromatin immunoprecipitation and luciferase reporter assay to screen and verify the transcription factors involved in the regulation of IRF1 expression. Using pattern recognition receptors (PRRs) activators and RNA interference to analyze the PRRs involved in the regulation of IRF1. Those results will help to analyze the mechanism of the up-regulated expression of IRF1 after PEDV infection, elucidate the mechanism of PRRs mediated host factors to activate IRF1, and reveal the molecular mechanism of PRRs recognize PEDV and mediate host factor up-regulating IRF1-BST2 pathway to inhibit PEDV proliferation. This project will increase the knowledge of host inhibiting virus proliferation by innate immune response and provide the theoretical basis and research direction for scientific prevention, control, and treatment of PED.