IFITMs限制病毒进入的分子机制及其免疫调控研究

项目名称： IFITMs限制病毒进入的分子机制及其免疫调控研究

项目编号： No.31472197

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： 李昌

作者单位： 中国人民解放军军事科学院军事医学研究院

项目金额： 82万元

中文摘要： 机体在与病毒长期的斗争实践中，宿主体内进化出了许多可以干扰病毒生命周期的细胞内抗病毒蛋白，即宿主限制因子（HRFs），通过HRFs介导的天然免疫是当前研究的重点和热点。干扰素诱导的跨膜蛋白（IFITMs）是目前发现的唯一一类可以抑制病毒进入的HRFs，该类分子的抗病毒作用自2009年《Cell》首次报道以来，目前已发现其至少对10个科20多种病毒的进入具有抑制作用，但其抗病毒机制尚不明晰。本研究拟以H7N9亚型禽流感假型病毒、痘苗病毒为切入点，通过建立病毒感染细胞模型，综合利用免疫沉淀-质谱、定量PCR、激光共聚焦、流式细胞术以及gain of funtion和loss of function等技术和方法，筛选鉴定IFITMs互作蛋白，开展其抗病毒进入的分子机制及其免疫调控研究，以期发现新的IFITMs作用分子，揭示其抗病毒信号通路，从而为该类分子的进一步临床应用奠定坚实理论基础。

中文关键词： 干扰素诱导跨膜蛋白；病毒；限制进入；分子机制；免疫调控

英文摘要： Host cells have evolved many intracellular antiviral proteins that can interfere with the viral life cycle, i.e., host restriction factors (HRFs). Innate immunity mediated by HRFs is a key and hot field in current research. Interferon-induced transmembrane proteins (IFITMs) are the only HRF reported can inhibit virus enter into cells previously. Since the first article about antiviral effect of IFITMs was illustrated in Cell in 2009, the potential inhibition of IFITMs has been reported at least 20 kinds of virus in 10 families. However, its antiviral mechanism is still unclear. This study intends to screen and identify IFITMs interaction proteins as well as demonstrate its antiviral mechanism and immunoregulation using H7N9 subtype influenza virus and vaccinia virus as a starting point. Many techniques and methods will be utilized in the experiment such as co-immunoprecipitation technology and mass spectrometric analysis (IP-MS), real-time quantitative polymerase chain reaction (qPCR), laser scanning confocal microscope (LSCM), flow cytometry (FCM), gain of function, loss of function, and so on. Through the above research, we hope that some new molecules interacted with IFITMs were found and identified, its antiviral signaling pathways is revealed, too. This work will lay good theoretical foundations for further clinical application of IFITMs.

英文关键词： IFITMs;virus;inhibit entry;molecular mechanisms;immunoregulation