柯萨奇病毒B3型入侵人神经细胞的动态过程及机制研究

项目名称： 柯萨奇病毒B3型入侵人神经细胞的动态过程及机制研究

项目编号： No.81501745

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 张源

作者单位： 中国科学院武汉病毒研究所

项目金额： 18万元

中文摘要： 柯萨奇病毒B3型（CVB3）是一种能引起多种疾病的重要病原体。它能够感染人类中枢神经系统（CNS），并在部分神经细胞中建立持续性感染，对患者造成长期毒害，目前尚无针对CVB3的有效防治方法。明确CVB3的入侵机制是设计新型抗病毒药物的基础，然而作为一种重要的嗜神经性病毒，CVB3对神经细胞的入侵机制却没有相关报道。本项目拟使用量子点标记技术及单颗粒病毒动态示踪技术，从单颗粒水平解析CVB3对两种神经细胞（CVB3能够引起急性感染的SK-N-SH及能够建立持续性感染的CCF-STTG1）的动态侵染过程及入侵机制，重点阐明CVB3的跨膜转运方式及囊泡运输过程，探讨CVB3对神经细胞的入侵机制与感染状态（急性感染或持续性感染）的潜在联系。本项目的完成，有助于我们深入理解CVB3引起神经性疾病的致病机制，也为抗CVB3药物的开发提供新信息和理论基础。

中文关键词： 柯萨奇病毒B3型；神经细胞；入侵机制；单颗粒动态示踪；量子点

英文摘要： Coxsackievirus B3（CVB3）is an important human pathogen which can induce a variety of diseases. CVB3 is able to infect human central nervous system (CNS) and establish persistent infection, causing permanent damage to patients. So far no cure is available for CVB3 infection. Despite the significance of CVB3 in human neurologic illnesses and the importance of infection mechanisms for antiviral research, no report about CVB3’s infection mechanism in neural cells can be found. We will use a Quantum-dots labeling and single particle trafficking strategy to study the infection mechanism of CVB3 in two neural cell lines, SK-N-SH cells in which CVB3 cause acute infection, and CCF-STTG1 cells in which CVB3 establish persistent infection, at the single virus particle level. The cellular entry and dynamic trafficking process of CVB3 in these two cell lines, especially the trans-membrane transport and vesicular transport process will be tracked, determined, and compared to elucidate the relativity between CVB3 cellular entry and virus infection state in neural cells. Our study will help to get a better understanding of CVB3-induced acute and chronic neuropathogenesis, and provide information and theoretical basis for anti-CVB3 research.

英文关键词： CVB3;neural cells;celluar entry mechanism;single particle trafficking;Quantum dots