手足口病是由肠道病毒感染引起的儿童急性传染病，柯萨奇病毒B5（CVB5）是引起儿童手足口病的重要病原体。我们前期研究发现，CVB5感染细胞后，细胞因子IL-1β、MCP-1和TFN-α含量减少，此外，NF-κB启动子活性、p65 mRNA及蛋白表达水平均明显降低，以上结果表明CVB5负调控宿主天然免疫应答NF-κB信号通路，我们推测是由于CVB5非结构蛋白（NSP）发挥了主要作用。本课题拟采用CVB5感染含有报告基因和NSP基因重组载体转染的细胞，通过检测启动子活性、mRNA和蛋白质水平，明确CVB5 NSP对NF-κB信号通路的调节机制；同时通过免疫共沉淀等筛选与CVB5 NSP相互作用的靶蛋白，分析靶蛋白对CVB5感染和复制的影响。本研究将阐明CVB5 NSP在感染细胞内调控天然免疫应答的分子机制，揭示病毒感染导致疾病的致病机理，为预防和治疗CVB5感染提供科学依据。

Hand, foot, and mouth disease (HFMD) is an acute infectious disease among young children by enterovirus infection, and coxsackievirus B5 (CVB5) is an important pathogen causing HFMD. Our previous research was found that after CVB5 infected cells, the levels of cytokines IL-1β, MCP-1 and TFN-α decreased. In addition, NF-κB promoter activity, p65 mRNA and protein expression were significantly reduced. The results showed that CVB5 inhibited the NF-κB signaling pathway and we speculate that CVB5 non-structural protein (NSP) plays a major role in mediation of host innate immune response. We will use cells transfect with a reporter gene and NSP gene recombinant vector by CVB5 infection and identify one of CVB5 NSPs which can regulate the NF-κB signaling on the promoter activity, mRNA copies and protein levels. At the same time, select the target proteins and its domain interacted with the NSP in the CVB5 infected cell by co-immunoprecipitation, and investigate the function of the target proteins on CVB5 infection and replication. Our research will elucidate the molecular mechanism in the regulation of host innate immune response by CVB5 NSP, and uncover the viral pathogenesis mechanism. It will provide scientific evidence for the prevention and treatment of CVB5 infection.