NLRX1和Sam68调控丙型肝炎病毒复制机制研究
发布时间:2021-11-15 13:46
丙型肝炎病毒(HCV)是一种重要的人类病原体,全世界有超过1.7亿人被感染,它可导致慢性肝炎、肝硬化、甚至肝癌。目前还没有有效针对丙型肝炎病毒的疫苗。HCV是一种单股正链RNA病毒,编码产生3种结构蛋白和7种非结构蛋白。HCV感染人类细胞后,受到宿主先天免疫应答的调控。病毒入侵宿主细胞后,模式识别受体RIG-I样受体识别病毒的病原相关分子模式(PAMPs),RIG-I和MDA5被激活后发生构象变化,激活定位在线粒体外膜上的接头蛋白MAVS,MAVS招募并激活IRF3和NF-kB,最终诱导I型、III型干扰素以及其他抗病毒细胞因子的产生。我们的研究发现,HCV上调肝细胞内的NLRX1蛋白水平。沉默NLRX1可抑制HCV复制,而过表达NLRX1则促进HCV复制和病毒蛋白的积累。在稳定沉默NLRX1的细胞系中感染HCV,I型干扰素、III型干扰素和干扰素诱导基因(ISGs)的mRNA水平都明显上升。进一步研究发现,NLRX1与接头蛋白MAVS结合,诱导MAVS泛素化降解。深入研究发现,NLRX1与PCBP2相互作用,并促进MAVS的K48位泛素化。除了HCV之外,NLRX1对其它RNA病毒诱...
【文章来源】:湖南大学湖南省 211工程院校 985工程院校 教育部直属院校
【文章页数】:115 页
【学位级别】:博士
【部分图文】:
TLR信号通路[15]
RLR信号传导通路[57]
宿主蛋白对先天性免疫通路的调控[110]
【参考文献】:
期刊论文
[1]Genes transactivated by hepatitis C virus core protein, a microarray assay[J]. Min Liu, Shu-Lin Zhang, Shu-Mei Lin, Department of Infectious Diseases, The First Affiliated Hospital, Medical College, Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China Jun Cheng, Yan Liu, Lin Wang, Qing Shao, Jian Zhang, Gene Therapy Research Center, Institute of Infectious Diseases, The 302 Hospital of PLA, Beijing 100039, China. World Journal of Gastroenterology. 2005(22)
[2]Transactivating effect of hepatitis C virus core protein: A suppression subtractive hybridization study[J]. Min Liu Shu-Lin Zhang Qian Yang,Department of Infectious Diseases,The First Hospital of Xi’an Jiaotong University,Xi’an 710061,Shaanxi Province,ChinaYah Liu Jun Cheng Lin Wang Qing Shao Jian Zhang,Gene Therapy Research Center,Institute of Infectious Diseases,302 Hospital of PLA,Beijing 100039,China. World Journal of Gastroenterology. 2004(12)
本文编号:3496896
【文章来源】:湖南大学湖南省 211工程院校 985工程院校 教育部直属院校
【文章页数】:115 页
【学位级别】:博士
【部分图文】:
TLR信号通路[15]
RLR信号传导通路[57]
宿主蛋白对先天性免疫通路的调控[110]
【参考文献】:
期刊论文
[1]Genes transactivated by hepatitis C virus core protein, a microarray assay[J]. Min Liu, Shu-Lin Zhang, Shu-Mei Lin, Department of Infectious Diseases, The First Affiliated Hospital, Medical College, Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China Jun Cheng, Yan Liu, Lin Wang, Qing Shao, Jian Zhang, Gene Therapy Research Center, Institute of Infectious Diseases, The 302 Hospital of PLA, Beijing 100039, China. World Journal of Gastroenterology. 2005(22)
[2]Transactivating effect of hepatitis C virus core protein: A suppression subtractive hybridization study[J]. Min Liu Shu-Lin Zhang Qian Yang,Department of Infectious Diseases,The First Hospital of Xi’an Jiaotong University,Xi’an 710061,Shaanxi Province,ChinaYah Liu Jun Cheng Lin Wang Qing Shao Jian Zhang,Gene Therapy Research Center,Institute of Infectious Diseases,302 Hospital of PLA,Beijing 100039,China. World Journal of Gastroenterology. 2004(12)
本文编号:3496896
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