项目名称: B组柯萨奇病毒衣壳蛋白VP1核定位的生物学意义
项目编号: No.31270198
项目类型: 面上项目
立项/批准年度: 2013
项目学科: 生物科学
项目作者: 赵文然
作者单位: 哈尔滨医科大学
项目金额: 78万元
中文摘要: B组柯萨奇病毒(CVB)是病毒性心肌炎、扩张型心肌病的主要病原,致病机制未阐明。某些RNA病毒衣壳蛋白可主动入核并损伤宿主细胞,是其致病机制之一。我们发现3型CVB衣壳蛋白VP1具有核定位信号(NLS),其他型别的VP1也有NLS相似序列,我们也发现VP1核定位可影响细胞的结构与功能,据此推测VP1核定位是CVB损伤宿主细胞以利自身复制的重要分子机制。本项目从三方向明确VP1核定位对CVB生物性状和致病性的作用:①确定CVB VP1的NLS序列;②对比CVB原型与VP1的NLS缺陷变异株的生物合成和复制,明确VP1核定位对CVB生物合成与复制等性状的影响;③对比原型和NLS缺陷型VP1对细胞的损伤作用,以及CVB原型和VP1 NLS缺陷型株对细胞和动物的致病差异,明确VP1核定位对CVB致病性的影响。本项目可能发现CVB调控和损伤宿主细胞的新机制,也为研发抗CVB药物提供新的分子靶点。
中文关键词: B组柯萨奇病毒;病毒核衣壳蛋白;VP1;核定位;细胞周期
英文摘要: Coxsackievirus B (CVB) is the major pathogen of viral myocarditis and dilated cardiomyopathy. The pathogenesis mechanism underlying CVB infection remains unclear. Some RNA viruses cause damages to the host cells by the active nuclear localization of their capsid proteins. Therefore, the nuclear localization of capsid proteins was one of the pathogenesis mechanisms for these viruses. We found that the capsid protein VP1 of CVB type 3 possessed a nuclear localization signal (NLS). In addition, other types of CVB had similar NLS sequences. We also observed that the nuclear localization of CVB VP1 disturbed the structure and function of the cells. Therefore, we hypothesized that the nuclear localization of VP1 may be one of the critical mechanisms for the damages to the host cells caused by CVB. VP1 nuclear localization may also be used by CVB to facilitate its own replication. This study aims to evaluate the effects of VP1 nuclear localization on the biology and pathogenicity of CVB: (1) Determine the NLS sequences of CVB VP1; (2) Determine the effects of VP1 nuclear localization on the biological properties of CVB by comparing the biosynthesis and replication of CVB protype and vairant with NLS-deficient VP1; (3) Determine the effects of VP1 nuclear localization on the pathogenicity of CVB by comparing the express
英文关键词: Coxsackievirus B;Viral capsid protein;VP1;Nuclear localization;Cell cycle