Cellular microenvironments facilitating the replication and propagation of flaviviruses

黄病毒是每年全球许多蚊子传播感染和许多人死亡的病原体。新出现的西尼罗河病毒(纽约株)是该病毒家族的成员，与澳大利亚地方性病毒昆津病毒有99%的氨基酸同源性。在病毒在细胞内生长的过程中，这些病毒为了自己的目的而诱导或重排细胞膜结构。这就是产生更多的病毒颗粒，以便重新感染其他细胞。以昆津病毒为模型，结合生物化学和电子显微镜的先进技术，我们首次确定这些膜结构是病毒RNA或遗传物质以及所涉及的病毒蛋白的表观复制部位。我们还观察了新的病毒颗粒是如何从受感染的细胞中出来的，并展示了一些药物如何阻止这种情况发生，从而限制它们的传播。这项研究将集中在感染细胞中膜结构是如何形成的。这项研究将确定病毒需要哪些细胞成分来帮助其传播。特别是被病毒捕获并移动到受感染细胞中不同位置的特定细胞蛋白和膜组件。这些明显的要求可能会让我们更好地理解入侵病毒和宿主细胞之间发生的复杂相互作用。我们的目标是使用新的和创新的显微技术直接显示活细胞内的感染过程。我们的另一个目标是确定感染对正常细胞的影响。问题是黄病毒感染是否会扰乱正常的细胞功能，如分泌等。了解这些过程，以及病毒RNA如何复制到新的RNA中以获得更多病毒颗粒，将有助于开发用于治疗这种病原性病毒组的抗病毒药物。

Flaviviruses are the agents of many mosquito-transmitted infections and many deaths globally each year. The emerging virus West Nile virus (strain New York) is a member of this virus family and shares 99% amino acid homology with the endemic Australian virus Kunjin virus. During virus growth in cells, cellular membrane structures are induced or rearranged by these viruses for their own purpose. That being the production of more virus particles for reinfection of other cells. Using Kunjin virus as a model, and advanced techniques in biochemistry and electron microscopy, we have identified for the first time these membrane structures as the apparent sites of replication of the viral RNA or genetic material, and of the viral proteins involved. We have also observed how new virus particles are able to get out of infected cells and shown how some drugs can prevent this occurring thus limiting their transmission. This research will focus on how the membrane structures are formed in infected cells. The research will determine what cellular components are required by the virus to help it propagate. In particular specific cellular proteins and membrane components that are captured by the virus and moved to different sites in the infected cells. These apparent requirements could possibly lead us to a greater understanding of the complex interactions that occur between the invading virus and the host cells. We aim to directly visualize the process of infection within living cells using new and innovative microscopic techniques. Another of our objectives is to determine the effects of infection on normal cells. The question being whether flavivirus infection disrupts normalcell fuctions like secretion etc. An understanding of these processes, and how the viral RNA is copied into new RNA for more virus particles, will assist in the development of antiviral drugs for treatment of this pathogenic group of viruses.