Cellular and microenvironmental factors controlling hepatitis Cvirus infection, examined by micro-proteomics of human liver tissues.

丙型肝炎病毒(HCV)是肝细胞癌的主要病因。目前已开发的抗丙型肝炎病毒药物仍存在副作用和耐药突变病毒等问题。在这项研究中，我们探索了一种基于人工抗丙型肝炎病毒应答的人性化抗丙型肝炎病毒治疗的新策略。我们检测了哪些蛋白在含有不同丙型肝炎病毒载量的肝组织中产生的差异增加了1000倍。比较时，分别从肝实质和肝间质中激光显微解剖获得肝组织标本。在高病毒载量和低病毒载量两组中，分别有90个和27个差异蛋白来自肝实质和基质。在高丙型肝炎病毒感染组中，亲病毒蛋白和抗病毒蛋白均上调。体外丙型肝炎病毒感染系统利用培养的细胞检测在病毒感染中功能未知的蛋白质。我们发现在高丙型肝炎病毒感染组中有两种蛋白上调：一种是参与丙型肝炎病毒感染进入步骤的丝氨酸蛋白酶，另一种是与丙型肝炎病毒分泌有关的高尔基蛋白。

Hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma. Anti-HCV drugs developed have still some problems such as side effects and drug-resistant mutant viruses. In this study, we investigated a new strategy of humane anti-HCV therapy based on human-made anti-HCV response. We examined which proteins were differentially produced in liver tissues containing different HCV loads by 1000 folds. When we compared them, we obtained liver tissue samples separately from liver parenchyma and stroma by laser microdissection. Ninety and 27 were differential proteins between the two groups of high and low viral loads, from the liver parenchyma and stroma, respectively. Both pro-viral and anti-viral proteins were up-regulated in the high HCV groups. Proteins which function was unknown in the viral infection were examined by the in vitro HCV infection system using cultured cells. We found two proteins up-regulated in the high HCV groups: a serine protease involved in the entry step of HCV infection and a golgi protein related to the secretion of HCV.