Flavivirus replication - biogenesis, ultrastructure and roles of induced membranes

黄病毒是许多蚊子传播感染的病原体，如脑炎和登革热，而丙型肝炎病毒是同一病毒家族的成员。病毒在细胞中增殖时，新的膜结构被诱导，这些膜结构代表复制事件发生的区域。利用昆津病毒（澳大利亚脑炎的一种病原体）作为模型，利用先进的生物化学和电子显微镜技术，我们已经确定了这些膜是病毒RNA或遗传物质的合成位点，以及所涉及的病毒蛋白质。这些组成了病毒复制复合体。这项研究将确定这些膜的起源，以及相关复制复合体的组成部分是如何组装的。病毒颗粒在细胞中的组装也正在使用类似的技术进行分析。目前，丙型肝炎病毒还不能可靠地在培养细胞中生长以用于研究目的，我们将尝试开发一种辅助系统来克服这个问题。了解这些过程，以及病毒RNA如何被复制成新病毒颗粒的子代RNA，可能有助于开发用于治疗慢性或持续性病毒感染（如丙型肝炎）的抗病毒药物。

Flaviviruses are the agents of many mosquito-transmitted infections such as encephalitis and dengue, and hepatitis C virus is a member of the same virus family. During virus multiplication in cells, new membrane structures are induced and these represent regions where the replication events occur. Using Kunjin virus, an agent of Australian encephalitis, as a model, and advanced techniques in biochemistry and electron microscopy, we have previously identified these membranes as the site of synthesis of the viral RNA or genetic material, and the viral proteins involved. These comprise the viral replication complex. The research will define the origin of these membranes, and how the components of the associated replication complex are assembled. Assembly of the virus particles in cells is also being analysed using similar technology. Hepatitis C virus cannot be reliably grown at present for research purposes in cultured cells, and we will attempt to develop a helper system to overcome the problem. An understanding of these processes, and how the viral RNA is copied into progeny RNA for new virus particles, may assist in the development of antiviral drugs for treatment of slow or persistent virus infections such as hepatitis C.