Cellular microenvironments facilitating the replication and propagation of flaviviruses

促进黄病毒复制和繁殖的细胞微环境

• 批准号: nhmrc : 351460
• 负责人: A/Pr Jason Mackenzie
• 金额: $ 33.69万
• 依托单位: La Trobe University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/cellular-microenvironments-facilitating-propagation-flaviviruses/99985
• 关键词: Cellular; microenvironments; facilitating; replication; propagation

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.

黄病毒是每年全球许多蚊子传播感染和许多死亡的病原体。新出现的病毒西尼罗河病毒（株纽约）是该病毒家族的成员，与澳大利亚地方性病毒昆津病毒具有99%的氨基酸同源性。在病毒在细胞中生长的过程中，细胞膜结构被这些病毒诱导或重排以达到它们自己的目的。这是生产更多的病毒颗粒再感染其他细胞。以昆津病毒为模型，利用生物化学和电子显微镜的先进技术，我们首次确定了这些膜结构是病毒RNA或遗传物质以及相关病毒蛋白质复制的明显位点。我们还观察到新的病毒颗粒如何能够从受感染的细胞中逃逸出来，并展示了一些药物如何阻止这种情况的发生，从而限制它们的传播。这项研究将集中在膜结构是如何在感染细胞中形成的。这项研究将确定病毒需要哪些细胞成分来帮助它繁殖。特别是被病毒捕获并移动到感染细胞不同部位的特定细胞蛋白和膜成分。这些明显的要求可能会使我们更好地了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可视化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破坏正常细胞的功能，如分泌等。了解这些过程，以及病毒RNA如何复制成新的RNA，以获得更多的病毒颗粒，将有助于开发抗病毒药物来治疗这种致病性病毒。