Molecular analyses of flavivirus RNA replication, encapsidation, and complementation

黄病毒是许多蚊子传播的感染如脑炎和登革热的病原体。丙型肝炎病毒是同一病毒家族的成员。以澳大利亚黄病毒Kunjin为模型，运用分子生物学、生物化学和电子显微镜等先进技术，SASVRC的黄病毒研究单位已成为黄病毒RNA复制和病毒感染细胞超微结构领域的国际领导者。本申请的目的是进一步推进我们对黄病毒RNA复制复合物如何组装，如何合成RNA以及这种RNA如何特异性包装以产生感染性病毒的理解。为了实现这些目标，我们将采用最先进的分子生物学技术的基础上与昆津病毒RNA的感染性互补DNA拷贝的操作。对黄病毒复制中这些机制的深入了解将有助于通过特异性靶向RNA复制和/或包装中的独特事件来设计有效的抗病毒药物。这可能有助于开发抗病毒药物，用于治疗澳大利亚其他高致病性黄病毒引起的感染，如登革热，日本脑炎和墨累谷脑炎，以及相关的丙型肝炎病毒。

Flaviviruses are the agents of many mosquito-transmitted infections such as encephalitis and dengue. Hepatitis C virus is a member of the same virus family. Using Australian flavivirus Kunjin as a model and advanced techniques in molecular biology, biochemistry and electron micriscopy, the Flavivirus Research Unit at SASVRC has established itself as an international leader in the area of flavivirus RNA replication and ultrastructure of virus-infected cells. The objectives of this application are to advance further our understanding of how the flavivirus RNA replication complex is assembled, how it synthesizes RNA and how this RNA is specifically packaged to produce infectious virus. To achieve these goals we will employ state-of-the-art molecular biology techniques based on manipulations with infectious complementary DNA copy of Kunjin virus RNA. The intimate understanding of these mechanisms in flavivirus replication should facilitate the design of efficient antiviral drugs by specifically targeting unique events in RNA replication and-or packaging. This may assist in the development of antiviral drugs for treatment of infections caused by other higly pathogenic flaviviruses in Australia, such as dengue, Japanese encephalitis and Murray Valley encephalitis, as well as of the related heptitis C virus.