Mechanism of superinfection exclusion by an RNA virus

该项目将研究被一种病毒感染的细胞如何对同一种或密切相关的病毒的二次感染产生抵抗力。这一过程被称为重复感染排除（SIE），被许多病毒使用，包括人类、动物和植物的重要病原体；它在病毒种群的发病机制和进化中起着重要作用，对治疗病毒感染具有明确的意义。例如，在植物中，有目的地接种无害病毒株可用于保护植物免受相关致病病毒的感染。尽管SIE具有重要意义，但人们对它的理解并不充分。因此，阐明SIE机制应具有广泛的科学影响，为制定控制人类和经济上重要的农作物的病毒性疾病的新战略提供必要的基础。该研究还将为博士后研究人员、研究生和本科生提供培训机会，并开发可用于促进年轻学生学习STEM的工具，从而产生强大的教育影响。柑橘tristeza病毒（CTV）是Closteroviridae科的一员，是高等植物中最大和最复杂的正链RNA病毒，本项目旨在阐明其SIE机制。CTV是研究SIE的一个有价值的模型系统，因为存在许多具有独特遗传特征的分离株。此外，CTV为在整个生物体水平上研究这一现象提供了可能性。该项目建立在观察的基础上，这些观察表明CTV的SIE通过一种独特的机制运作，该机制涉及多种病毒编码因子。先进的遗传工具将与创新技术和超微结构方法相结合，用于研究蛋白质-蛋白质和rna -蛋白质相互作用。该项目产生的材料和数据将公开供研究和教育使用。例如，作为研究的一部分，荧光标记的病毒使病毒在受感染树木中的运动可视化，从而成为吸引年轻学生的极好的学习工具。综上所述，该研究结果有望为CTV对SIE的机制提供新的见解，并促进对病毒-宿主相互作用的理解。

This project will study how cells infected by one virus become resistant to a secondary infection by the same or closely related virus. This process, called superinfection exclusion (SIE), is used by many viruses, including important pathogens of humans, animals, and plants; it plays an important role in the pathogenesis and evolution of viral populations and has clear implications for treating viral infections. For instance, in plants, purposeful inoculation with a harmless virus strain can be used to protect plants from infection by related pathogenic viruses. In spite of its significance, the phenomenon of SIE is not well understood. Thus, elucidation of the SIE mechanism(s) should have broad scientific impact by providing a necessary foundation for development of new strategies to control viral diseases of humans and economically important agricultural crops. The research will also have strong educational impact by offering training opportunities for postdoctoral researchers, graduate and undergraduate students and by developing tools that can be used for promoting STEM learning by younger students. This research project aims to elucidate the mechanism of SIE of Citrus tristeza virus (CTV), a member of the family Closteroviridae, which includes the largest and most complex positive-strand RNA viruses of higher plants. CTV represents a valuable model system for studying SIE, due to the existence of numerous well-characterized isolates with distinctive genetic characteristics. Furthermore, CTV provides a possibility for studying this phenomenon at the whole organism level. The project builds on observations suggesting that SIE by CTV operates by a unique mechanism, which involves multiple virus-encoded factors. Advanced genetic tools will be combined with innovative techniques and ultrastructural approaches for studying protein-protein and RNA-protein interactions. Materials and data produced by the project will be openly accessible for research and educational uses. For example, the fluorescently-tagged viruses used as part of the research enable visualization of virus movement in infected trees and thus serve as an excellent learning tool for engaging young students. Taken together, the results of the research are expected to produce new insights into the mechanism of SIE by CTV, as well as to advance understanding of virus-host interactions.