細胞因子PTB對C型肝炎病毒複製機制的探討; The function role of polypyrimidine tract-binding protein in HCV replication

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Title:	細胞因子PTB對C型肝炎病毒複製機制的探討;The function role of polypyrimidine tract-binding protein in HCV replication
Authors:	葉維洲;Wei-Zhou Yeh
Contributors:	中國醫藥大學醫學研究所
Date:	1994
Issue Date:	2009-12-24 10:59:19 (UTC+8)
Abstract:	C型肝炎病毒屬於黃病毒科，是造成非A非B型肝炎的主要致病原。C型肝炎病毒基因體為一條單股正向的RNA分子，全長9.6 kb，可產生至少十個結構與非結構性病毒蛋白質。非結構性蛋白質NS5B是RNA聚合?(RNA-dependent RNA polymerase, RdRp)，它是病毒複製機制中最重要的酵素。細胞因子PTB會和C型肝炎病毒非轉譯區產生交互作用，不論是5’端或是3’端。此外，實驗室從in vivo 和in vitro的實驗結果得知PTB會和NS5B的交互作用。因此PTB可能參與病毒RNA合成。為瞭解PTB在C型肝炎病毒複製機制中的角色，我們藉由即時反轉錄聚合?連鎖反應(real-time RT-PCR)和西方墨點法分析PTB對HCV replicon 細胞的影響。PTB會抑制HCV RNA的合成以及非結構蛋白質的表現。除此之外，PTB 靠近胺基端的蛋白質能明顯的抑制HCV RNA的合成。最後，我們看到PTB和NS5B在細胞質共同表現。綜合實驗結果，PTB會藉由和NS5B的交互作用影響HCV病毒的RNA和蛋白質的合成。; Hepatitis C virus (HCV) belongs to the Flaviviridae . It is the major cause of post-transfusion non-A, non-B hepatitis. HCV contains a positive single-stranded RNA genome of 9.6 kb that encodes at least 10 structural and nonstructrual viral proteins. The NS5B is an RNA-dependent RNA polymerase (RdRp) that serves as a key player to synthesize viral RNA. PTB was shown to interact with HCV 5’- and 3’- untranslated regions. In addition, our previous data showed that PTB could interact with HCV NS5B in vivo and in vitro. Therefore, PTB should involve in HCV RNA synthesize. To understand the functional role of PTB in HCV replication, we analyzed the effects of PTB on HCV RNA synthesis using real-time RT-PCR and Western blot analysis in HCV replicon cells. PTB appears to partially repress HCV RNA synthesis, and HCV nonstructural protein expression. In addition, N-terminal of PTB dramatically inhibit in HCV RNA synthesis. Finally, we demonstrate that PTB and HCV NS5B colocalize in cytoplasma region. Taken together, PTB could affect HCV RNA synthesis through interacting with HCV NS5B.
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