Riboregulation of RNA Virus Replication

RNA病毒对动植物的健康构成严重威胁。我的研究计划的目标是详细了解这种传染病病原体在繁殖周期中的关键步骤。我们的研究是利用番茄属病毒的原型成员番茄丛矮病毒进行的，番茄丛矮病毒是目前研究得最深入的致病RNA病毒。我们的研究集中在三个不同的分子过程上，这三个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’多聚(A)非依赖尾的翻译；(Ii)病毒基因组的复制；(Iii)病毒亚基因组mRNAs的RNA模板转录。在病毒感染期间，这些不同的过程被仔细地协调，病毒和宿主蛋白都密切参与了这种控制。因此，对致病RNA病毒的研究大多集中在这些蛋白因子上。相反，我从一种非常规的角度来处理调控问题，在这种观点中，病毒RNA基因组被视为协调病毒相关分子过程的数量、时间和空间方面的积极参与者。坦率地说，我的研究探索了“病毒核转录调控”--病毒RNA如何主动地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，将包括计算、原子、生化、分子、遗传、细胞和生物水平的分析。产生的数据将被整合并用于建立一个全面的病毒感染核转录调控的多维模型。了解病毒核转录调控很重要，因为它代表了一种独特的基本类型的调控系统。此外，对这一过程的了解通过生物技术对社会具有明显的潜在益处--例如，通过开发针对和抑制核调节元件活性的新型抗病毒策略，或者通过调节它们的活性来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.