The Cellular Actin Network and Virus Replication

细胞肌动蛋白网络和病毒复制

• 批准号: 1517751
• 负责人: Peter Nagy
• 金额: $ 57万
• 依托单位: University of Kentucky Research Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1517751&HistoricalAwards=false
• 关键词: Cellular; Actin; Network; Virus; Replication

This project will dissect how plant viruses interact with the actin cytoskeleton, one of the intracellular protein scaffolds along which much molecular movement (trafficking) occurs. Viruses appear to target the actin network to reprogram cellular pathways so that they support the virus life cycle instead of performing normal cellular functions. It has been observed that viruses modify the functionality of the actin network, thereby dramatically reorganizing the infected cells to support viral replication. A potential societal benefit of this research is a deeper understanding of virus-host interactions that could lead to potent new anti-viral approaches. In addition, this work will provide training for graduate students and a postdoctoral fellow and will provide opportunities for high school students to participate in supervised research and present their results at high school science competitions.The project will exploit the new discovery that plant viruses target cellular cofilin, a major regulator of the actin network. The research will address the questions: How does a virus exploit cofilin to interfere with the actin network? How does actin organization control viral replication in cells? The project will take advantage of yeast as a model host for viruses, allowing the testing of well-characterized cofilin and actin mutants in virus replication. In vitro assays with purified components and microscopy-based analysis of the actin network in yeast and plant cells accumulating viruses will be used to unravel the steps in the viral replication process that are affected by actin. Proteomic analysis of the viral replication complex will determine which of the host proteins that are subverted by viruses are regulated by the actin network.

本计画将剖析植物病毒如何与肌动蛋白细胞骨架相互作用，肌动蛋白细胞骨架是细胞内蛋白质的骨架之沿着，许多分子运动（运输）发生。病毒似乎以肌动蛋白网络为目标，重新编程细胞通路，使它们支持病毒的生命周期，而不是执行正常的细胞功能。已经观察到，病毒改变肌动蛋白网络的功能，从而显著地重组受感染的细胞以支持病毒复制。 这项研究的一个潜在的社会效益是更深入地了解病毒与宿主的相互作用，这可能导致有效的新的抗病毒方法。此外，该项目还将为研究生和博士后提供培训，并为高中生提供参与监督研究并在高中科学竞赛中展示成果的机会。该项目将利用植物病毒靶向细胞cofilin的新发现，cofilin是肌动蛋白网络的主要调节剂。这项研究将解决以下问题：病毒如何利用cofilin来干扰肌动蛋白网络？肌动蛋白组织如何控制细胞中的病毒复制？该项目将利用酵母作为病毒的模型宿主，允许在病毒复制中测试良好表征的cofilin和肌动蛋白突变体。用纯化的组分进行体外测定，并对积累病毒的酵母和植物细胞中的肌动蛋白网络进行基于显微镜的分析，将用于解开受肌动蛋白影响的病毒复制过程中的步骤。病毒复制复合物的蛋白质组学分析将确定哪些被病毒破坏的宿主蛋白质受肌动蛋白网络的调节。