Riboregulation of RNA Virus Replication

RNA病毒对植物和动物的健康构成严重威胁。 我的研究计划的目标是获得在这种类型的传染性病原体的生殖周期的关键步骤的详细了解。 我们的研究是使用番茄丛矮病毒属的原型成员进行的，番茄丛矮病毒是目前深入研究的致病性RNA病毒。 我们的研究集中在三个不同的分子过程，是成功感染宿主植物所必需的。 这些事件是：（i）病毒蛋白的5'帽-和3'聚（A）-尾-非依赖性翻译;（ii）通过病毒编码的RNA依赖性RNA聚合酶复制病毒基因组;和（iii）病毒亚基因组mRNA的RNA模板化转录。这些不同的过程在病毒感染期间被仔细地协调，并且病毒和宿主蛋白质都密切参与这种控制。 因此，对致病性RNA病毒进行的大部分研究都集中在这些蛋白质因子上。 相反，我从一个不太传统的角度来探讨调控问题，即病毒RNA基因组被视为病毒相关分子过程中定量、时间和空间方面的积极参与者。 简单地说，我的研究探索了“病毒核糖核酸调节”-病毒RNA如何主动调节和协调感染过程。我们将确定病毒RNA元件与其他RNA和/或蛋白质因子共同作用的机制。 这些研究将是非常全面的，将包括在计算，原子，生物化学，分子，遗传，细胞和有机体水平的分析。 所产生的数据将被整合并用于构建病毒感染的核糖核酸调控的综合多维模型。理解病毒核糖核酸调控是重要的，因为它代表了一种独特的和基本的调控系统。 此外，这一过程的知识通过生物技术对社会具有明显的潜在益处-例如，通过开发靶向和抑制核糖核酸调节元件的活性的新型抗病毒策略，或通过调节其活性以优化基于病毒的蛋白质表达载体。

RNA viruses represent a serious threat to the health of plants and animals. The goal of my research program is to gain a detailed understanding of critical steps in the reproductive cycle of this type of infectious agent. Our studies are carried out using the prototypical member of the genus Tombusvirus, Tomato bushy stunt virus, which is currently an intensively studied pathogenic RNA virus. Our research focuses on three distinct molecular processes that are essential for successful infection of host plants. These events are: (i) 5' cap- and 3' poly(A)-tail-independent translation of viral proteins; (ii) replication of the viral genome by a virally-encoded RNA-dependent RNA polymerase; and (iii) RNA-templated transcription of viral subgenomic mRNAs. These distinct processes are carefully coordinated during viral infections and both viral and host proteins are intimately involved in this control. Accordingly, most of the research carried out on pathogenic RNA viruses has focused on these protein factors. In contrast, I have approached the question of regulation from a less conventional perspective in which the viral RNA genome is viewed as an active participant in orchestrating quantitative, temporal, and spatial aspects of virus-related molecular processes. Stated plainly, my research explores "viral riboregulation" - how viral RNA actively modulates and coordinates the infectious process. We will determine the mechanisms by which viral RNA elements operate in conjunction with other RNA and/or protein factors. These studies will be exceptionally comprehensive and will include analyses at computational, atomic, biochemical, molecular, genetic, cellular, and organismal levels. The data generated will be integrated and used to build a comprehensive multi-dimensional model of riboregulation for viral infection. Understanding viral riboregulation is important as it represents a unique and fundamental type of regulatory system. Additionally, knowledge of this process has clear potential benefits to society via biotechnology - e.g. through the development of novel antiviral strategies that target and inhibit the activity of riboregulatory elements or by regulating their activities to optimize virus-based protein expression vectors.