Key role of the multifunctional translation elongation factor in virus replication

多功能翻译延伸因子在病毒复制中的关键作用

• 批准号: 1122039
• 负责人: Peter Nagy
• 金额: $ 80.68万
• 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: 2012
• 资助国家: 美国
• 起止时间: 2012-01-15 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1122039&HistoricalAwards=false
• 关键词: Key; role; multifunctional; translation; elongation

Intellectual Merit: Replication is the central step in the infectious cycles of RNA viruses, which cause many devastating diseases in plants, animals and humans. These viruses replicate inside the infected cells by co-opting an unknown number of host proteins and reprogramming several cellular pathways. In spite of the significance of host proteins in viral pathogenesis, our current knowledge about host factors subverted for virus replication is incomplete. This project is aimed at addressing the role of the multifunctional host-coded translation elongation factor 1A (eEF1A), which is a permanent resident in the viral replicase complex and plays a key role in Tomato bushy stunt virus (TBSV) replication. The research will unravel the functions of eEF1A using innovative approaches including yeast and plant assays developed for tombusviruses, as well as the powerful cell-free TBSV replication assay in yeast extracts. This research will likely lead to major new insights into virus replication and viral pathogenesis and will have a considerable impact on our understanding of the mechanism that transforms the host cells into "viral factories". Since eEF1A likely affects replication of a large number of plant and animal viruses, major progress with tombusviruses would be highly advantageous to study of other viruses as well. Broader Impacts: High school and undergraduate students will actively participate in the research. Students will be exposed to highly innovative research, thus providing them an invaluable learning experience. This research will promote interdisciplinary (plant pathology, biochemistry, cell biology, genetics) learning. The research also includes mentoring for postdoctoral researchers and preparing them for a scientific career in academia or industry. Pioneering research on tombusvirus replication will immensely help other scientists working with less tractable, but devastating viral pathogens for which similar studies are currently not yet feasible. Dissection of the role of eEF1A in viral pathogenesis and disease development will facilitate future antiviral approaches and treatments to reduce the effect of viral diseases in agriculture.

智力优势：复制是RNA病毒感染循环的核心步骤，RNA病毒在植物、动物和人类中引起许多毁灭性疾病。这些病毒通过选择未知数量的宿主蛋白质并重新编程几种细胞途径在感染细胞内复制。尽管宿主蛋白质在病毒发病机制中具有重要意义，但我们目前对病毒复制破坏的宿主因子的认识是不完整的。该项目旨在解决多功能宿主编码的翻译延伸因子1A（eEF1A）的作用，该因子是病毒复制酶复合物中的永久居民，在番茄丛矮病毒（TBSV）复制中起关键作用。该研究将使用创新方法揭示eEF1A的功能，包括为tombusviruses开发的酵母和植物测定，以及酵母提取物中强大的无细胞TBSV复制测定。这项研究可能会导致对病毒复制和病毒发病机制的重大新见解，并将对我们理解将宿主细胞转化为“病毒工厂”的机制产生相当大的影响。由于eEF1A可能影响大量植物和动物病毒的复制，因此，对tombusviruses的重大进展也将非常有利于对其他病毒的研究。 更广泛的影响：高中和本科生将积极参与研究。学生将接触到高度创新的研究，从而为他们提供宝贵的学习经验。这项研究将促进跨学科（植物病理学，生物化学，细胞生物学，遗传学）的学习。该研究还包括指导博士后研究人员，并为他们在学术界或工业界的科学生涯做好准备。对tombusvirus复制的开创性研究将极大地帮助其他科学家研究不太容易处理但具有破坏性的病毒病原体，目前类似的研究尚不可行。剖析eEF1A在病毒发病机制和疾病发展中的作用将有助于未来的抗病毒方法和治疗，以减少病毒性疾病在农业中的影响。