巨噬细胞微环境响应不同毒力病毒株侵染的差异调控机制研究

项目名称： 巨噬细胞微环境响应不同毒力病毒株侵染的差异调控机制研究

项目编号： No.31470535

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生态学

项目作者： 宁蓬勃

作者单位： 西安电子科技大学

项目金额： 82万元

中文摘要： 巨噬细胞是机体重要的免疫细胞，往往也是病毒攻击的靶细胞，受到侵染后成为病毒携带者，以致慢性感染发生。缺少对病毒入侵最早期信号事件的了解是当前病毒分子生态学研究的瓶颈。细胞微环境作为病毒实现感染的物质基础，不同毒力的病毒对细胞微环境的早期改变具有本质差异，以致形成不同感染结局。本项目针对巨噬细胞微环境应对不同毒力病毒侵染的早期差异改变开展研究，通过已建立的数字基因表达谱数据库，在转录水平开展不同组间差异基因的个性化分析，明确巨噬细胞信号通路中可能的重要调控基因；应用基因RNAi和过表达技术验证相关基因功能；在细胞周期、凋亡、JAK-STAT信号通路三个维度解析巨噬细胞应对不同毒力病毒的差异性应答机制，同时揭示关键基因对病毒复制的反向调控作用。从而在病毒入侵、共存、反馈响应这3个巨噬细胞应对侵染的典型时期阐明其耐受病毒感染的微生态进程和调控机制，为控制并终止病毒慢性感染提供切实可行的操作依据。

中文关键词： 分子机制；微生物生态学；巨噬细胞；病毒感染；分子生态

英文摘要： Macrophages are important immune cells in the body. However, it is often be attacked as target cells in the viral infection and become carriers of the virus, which would result in the occurrence of chronic infection. It is a bottleneck for virus molecular ecology studies that lacking of understanding in the early signaling events involved in process of virus infection. Cellular microenvironment is the material basis for virus to achieve its infection. There is an essential difference for viruses of differing virulence to impairing cellular microenvironment which bring out different infection outcomes. So, this project pays close attention to different responses of macrophage microenvironment to viral infection of differing virulence. Through established digital gene expression profiles (DGE), the differential expression genes of groups are screened, and key genes would be obtained by analyzing their important regulatory role to signaling pathway in macrophages. Next, RNAi and gene over-expression testing technique will be carried out to verify the function of key genes. Research aimed at the cell cycle, apoptosis and JAK-STAT signaling pathway of macrophage will be carried out to analyze different response mechanism in macrophages to viral infection of differing virulence while the role of some key genes in affecting viral replication will be clarified. This work would illuminate a potential micro-ecology process and regulatory mechanisms for macrophages tolerating virus infection in three typical stages, invasion, commensalism and feedback response, which would provide practical basis for control and termination of chronic viral infection.

英文关键词： molecular mechanism;microbial ecology;macrophage;viral infection;molecular ecology