人類MCPIP1抑制C型肝炎病毒感染之研究

Taipei Medical University Institutional Repository > 醫學科技學院 > 醫學檢驗暨生物技術學系所 > 博碩士論文 > Item 987654321/54084

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题名:	人類MCPIP1抑制C型肝炎病毒感染之研究 The study of human MCPIP1 inhibits hepatitis C virus infection
作者:	鄭蕙瑩 Cheng, Hui-Ying
关键词:	C型肝炎病毒;人類MCPIP1蛋白質;Hepatitis C virus;human MCPIP1
日期:	2012-07-18
上传时间:	2018-11-16 11:32:53 (UTC+8)
摘要:	Monocyte chemotactic protein-1-induced protein 1 (MCPIP1)，也被稱為Zc3h12a，在負向調控發炎反應上扮演一個重要的角色。MCPIP1蛋白質包含著高度保存性的CCCH-type zinc finger domain與 Nedd4-BP1, YacP Nuclease (NYN) domain，分別具有RNA binding及ribonuclease (RNse) activity的特性。在本篇研究中，我們發現C型肝炎病毒(Hepatitis C virus, HCV)感染Huh-7.5細胞會引發MCPIP1的表現。藉由慢病毒轉染細胞過度表現MCPIP1蛋白質可以抑制HCV的感染及HCV RNA的複製。藉由不同MCPIP1突變型探討MCPIP1功能性domain是否參與在抗HCV的機制，研究結果指出RNase、RNA binding與oligomerizaiton參與MCPIP1抗HCV的機制，而其本身的Deubiquitinase活性與MCPIP1抗HCV的機制無關。由viral RNA binding與in vitro cleavage assay的實驗結果指出，MCPIP1藉由Mg2+¬-dependent的方式，直接與HCV RNA結合並降解病毒RNA。綜合我們的實驗結果建議，MCPIP1為未報導過的HCV所誘發的宿主細胞因子，能藉由直接與HCV RNA結合，並以本身具有的RNase降解HCV RNA，以抑制HCV RNA的複製。 Monocyte chemotactic protein-1-induced protein 1 (MCPIP1), also name as Zc3h12a, has been identified to play an important role in negative regulation of the cellular inflammatory responses. MCPIP1 protein has a highly conserved CCCH-type Zinc finger domain and Nedd4-BP1, YacP Nuclease (NYN) domain which are involved in RNA-binding and ribonuclease (RNase) activity, respectively. In this study, we found that Hepatitis C virus (HCV) infection can induce the expression of MCPIP1 protein in Huh-7.5 cells. Overexpression of MCPIP1 by lentiviral transduction inhibited HCV infection in Huh-7.5 cells and HCV RNA replication in replicon cells. The anti-HCV mechanism of MCPIP1 by various mutants in functional domains showed that its RNase, RNA binding, and oligomerization but not DUB activity are involved in the antiviral activity against HCV. Viral RNA binding and in vitro cleavage assays indicated that MCPIP1 binds to and degrades HCV viral RNA in an Mg2+-dependent manner. Our findings demonstrate that human MCPIP1 is a novel HCV-induced host factor, which acts as an RNase to suppress HCV replication through viral RNA binding and degradation.
描述:	碩士指導教授-梁有志共同指導教授-林時宜委員-葉添順委員-劉俊仁委員-林宜玲
数据类型:	thesis
显示于类别:	[醫學檢驗暨生物技術學系所] 博碩士論文

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