INFECTION AND REPLICATION OF NATURALLY OCCURRING HEPATITIS C VIRUS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 全球约有1.7亿人感染丙型肝炎病毒。然而，丙型肝炎病毒的生命周期被部分理解，因为它不可能在培养中感染人类肝细胞。目前的Huh-7系统使用在肝细胞癌细胞中表达的克隆的、合成的丙型肝炎病毒RNA来产生假颗粒，但这些细胞不能被从感染患者那里获得的自然产生的丙型肝炎病毒感染。在这里，我们描述了一种允许在丙型肝炎病毒感染者血液中自然产生的丙型肝炎病毒基因1、2、3和4感染的人肝细胞培养。该培养系统模拟了人类感染丙型肝炎病毒的生物学和动力学，并产生了可感染新生人类肝细胞的感染性病毒粒子。这种培养系统应该是对现有系统的补充，并可能有助于了解丙型肝炎病毒的生命周期，它对自然宿主细胞、肝细胞的影响，以及新疗法和疫苗的开发。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hepatitis C virus (HCV) infection afflicts about 170 million individuals worldwide. However, the HCV life cycle is partially understood because it has not been possible to infect human hepatocytes in culture. The current Huh-7 systems use cloned, synthetic HCV RNA expressed in hepatocellular carcinoma cells to produce pseudo particles, but these cells cannot be infected with naturally occurring HCV obtained from infected patients. Here, we describe a human hepatocyte culture permissible to the infection with naturally occurring HCV genotypes 1, 2, 3 and 4 in the blood of HCV-infected patients. The culture system mimics the biology and kinetics of HCV infection in humans, and produces infectious virions that can infect na¿ve human hepatocytes. This culture system should complement the existing systems, and may facilitate the understanding of the HCV life cycle, it effects in the natural host cell, the hepatocyte, as well as the development of novel therapeutics and vaccines.