Key role of the multifunctional translation elongation factor in virus replication

智力优势：复制是RNA病毒感染周期的核心步骤，它在植物、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和重新编程一些细胞途径在受感染细胞内复制。尽管宿主蛋白在病毒发病机制中具有重要意义，但我们目前对破坏病毒复制的宿主因子的了解是不完整的。该项目旨在研究多功能宿主编码翻译延伸因子1A （eEF1A）的作用，该因子是病毒复制酶复合体中的永久居民，在番茄丛矮病毒（TBSV）的复制中起关键作用。该研究将利用创新方法揭示eEF1A的功能，包括针对tombusvirus开发的酵母和植物试验，以及酵母提取物中强大的无细胞TBSV复制试验。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tombusvirus研究的重大进展将对其他病毒的研究非常有利。更广泛的影响：高中生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。这项研究还包括指导博士后研究人员，为他们在学术界或工业界从事科学事业做准备。对瘤状病毒复制的开创性研究将极大地帮助其他科学家研究不易处理但具有破坏性的病毒病原体，这些病毒病原体目前尚不可行。分析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，以减少病毒性疾病对农业的影响。

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.