PLC/钙离子信号在BoHV-1感染中的作用研究

项目名称： PLC/钙离子信号在BoHV-1感染中的作用研究

项目编号： No.31472172

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 水产学、兽医学

项目作者： 朱礼倩

作者单位： 扬州大学

项目金额： 72万元

中文摘要： BoHV-1感染引起呼吸道炎症反应对全世界养牛业造成巨大经济损失。TNF-a和IL-1β等促炎性细胞因子是介导BoHV-1引起炎症反应发生的重要因素，但BoHV-1诱导该细胞因子产生的机理尚未阐明。已证实钙离子能调节细胞因子表达，前期研究发现该病毒需要PLC、钙离子和PI3K信号协助感染，故推测:BoHV-1侵入细胞过程经PLC依赖和/或非PLC依赖的机制激活胞内钙离子信号，该信号协助病毒复制并通过激活MAPK和/或PI3K而激活NF-κB分子从而介导TNF-a及IL-1β合成；通过自分泌作用该细胞因子激活胞内钙离子信号与病毒诱导的钙离子信号协同调节病毒复制和炎症因子大量产生。如果假设被证实将发现病毒诱导促炎性细胞因子表达的新机制，为证实并完善该假说将对BoHV-1与PLC/钙离子/NF-κB信号互作的分子机制进行系统研究。本课题将首次系统阐明BoHV-1诱导促炎性细胞因子表达的分子机理。

中文关键词： 牛疱疹病毒1型；磷脂酶C；钙离子；促炎性细胞因子；炎症反应

英文摘要： Bovine herpesvirus-1 (BHV-1), an important pathogen of cattle caused significant economic losses to the livestock industry, worldwide, due to the virus induced respiratory inflammation. Cytokines are the main orchestrators of the inflammatory cascade that triggers acute respiratory injury.However,the mechanism for the viral-induceed production of proinflammatory cytokines is unknown.It was evidenced that calcium is a regulator for the expression of some cytokines.Our primary data indicated that PLC, Calcium and PI3K signalings are required for BoHV-1 efficient replication. In this proposal, as to the mechanism of BoHV-1 induced proinflammatory cytokines expression, we put up a hypothesis. The process of BoHV-1 enter cells activates Calcium signaling pathway with PLC-dependent or -independent manner. The activated Calcium signaling contributes to the virus propagation, and triggers NF-κB signaling through activating MAPK and/or PI3K pathway(s). The activated NF-κB signaling initiates the expression of proinflammatory cytokines TNF-a and IL-1β, in respond to the virus infection. The cytokines secreted in an autocrine manner will mobilize intracellular Calcium. So the intracellular calcium signaling moblized by both virus infection and proinflammatory cytokines would synergically promote the virus replication and proinflammatory cytokines expression. To verify this hypothesis we would focus on elucidating the interaction between PLC/Calcium/NF-κB signaling and BoHV-1 infection. Once approved, we could present a new model by which proinflammatory cytokines are regulated in BoHV-1 infection. So this study would provide us, for the first time a novel insight about the regulation of BoHV-1 infection and the virus induced generation of proinflammatory cytokines via PLC/Calcium/NF-κB signaling.

英文关键词： BoHV-1;PLC;Calcium;proinflammatory cytokine;inflammation