| 摘要: | C 型肝炎病毒(hepatitis C virus, HCV) 為輸血後非A 非B 型肝炎的重要致病原，感染後易轉變成慢性肝炎，並與肝癌形成具有密切的關係。有關 C 型肝炎病毒的致病機轉尚不清楚，臨床上也還未找到有效的治療及預防策略，因此瞭解其複製機轉為一重要課題。 C 型肝炎病毒的基因體為一正向單股線狀的 RNA 分子，約9.5 kb，除5' 端及 3' 端非轉譯區外， 只含有一個開放編閱架構，可轉譯出一條約 3010 個胺基酸的多蛋白質先驅分子，經由宿主和病毒自身蛋白切割成結構性蛋白質 (core, E1, E2, p7)與非結構性蛋白質(NS2, NS3, NS4A, NS4B, NS5A, NS5B)。其中NS5B 蛋白質已證實為C 型肝炎病毒進行複製的主要酵素，可與病毒基因體 3' 端結合，進行病毒起始複製。細胞因子 PTB 曾被證實可結合於病毒基因體 5' 端及 3' 端，而本實驗室則證明，細胞因子 PTB可與NS5B 蛋白質結合。本研究進一步發現細胞因子 PTB 可抑制HCV蛋白質及RNA的合成。
Hepatitis C virus (HCV) is a single-stranded RNA virus and is a major pathogen for non-A, non-B hepatitis. Infection with HCV may sequentially develop chronic hepatitis and is closely related to the formation of hepatocellular carcinoma. At present, the mechanism involved in the pathogenic effect of HCV is still not clear and no protective vaccine and efficacy treatment strategy are available. Structural analysis of the 9.5 kb HCV RNA genome indicates that, in addition to the 5'- and 3'- untranslation regions, there is only one open reading frame encoding an approximate 3010 amino acid polyprotein precursor that can be cleaved by the proteases originated from HCV and host cells into structural (core, E1, E2, and p7) and non-structural (NS2, NS3, NS4A, NS4B, NS5A, and NS5B) proteins. Among the non-structural proteins, the NS5B protein has been shown recently to serve as the HCV replicase that binds to the 3'-end of the HCV genome and initiates virus replication. We have demonstrated recently NS5B binds to a cellular protein PTB. In this study, we found that PTB inhibit HCV translation and RNA synthesis. |
