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HCV药物仍存在一些问题，如副作用和耐药变异病毒。在这项研究中，我们探讨了一种新的策略，人性化的抗-HCV治疗的基础上，人为的抗-HCV反应。我们研究了哪些蛋白质在含有不同HCV载量的肝组织中差异产生1000倍。在比较时，我们采用激光显微切割技术分别从肝实质和间质中获取肝组织标本。90和27之间的差异蛋白质组的高和低病毒载量，从肝实质和间质，分别。在高HCV组中，前病毒和抗病毒蛋白均上调。使用培养的细胞，通过体外HCV感染系统检查在病毒感染中功能未知的蛋白质。我们发现两种蛋白质在高HCV组中上调：一种参与HCV感染进入步骤的丝氨酸蛋白酶和一种与HCV分泌相关的高尔基体蛋白。

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.