Riboregulation of RNA Virus Replication

RNA病毒对植物和动物的健康构成严重威胁。我们研究项目的目标是详细了解这种传染性病原体繁殖周期的基本步骤。我们的实验室专注于“病毒核糖调节”领域-病毒RNA基因组中的病毒RNA元件调节感染过程关键步骤的机制。我们的研究利用了植物病毒家族Tombusviridae的成员，这是一种小的球形病毒，含有单链，正感测（即信使感测）RNA基因组，并在多种重要的作物植物中引起疾病。我们重点研究了这个家族的原型成员，番茄丛矮病毒（TBSV），它代表了在分子水平上理解感染过程的一个很好的模型病毒。为了确定病毒RNA元件的功能，我们将使用不同的方法，包括计算、生化、分子和细胞技术。这些TBSV RNA基因组的研究结果将使我们更好地了解这台多功能RNA机器，并建立一个全面的病毒感染核素调控的多维模型。此外，我们将把我们的基因组RNA结构-功能分析扩展到Tombusviridae家族的其他属，以鉴定新的病毒RNA元素并确定这些结构特征如何分化和进化。了解病毒核素调节的重要性有几个原因。首先，它代表了许多病毒使用的一种基本而独特的调节策略，因此我们的结果可能与其他RNA病毒，甚至可能与细胞mrna相关。其次，我们在这一领域的工作有助于促进一个新概念，即除了局部RNA元件外，病毒RNA基因组的整体结构对控制病毒过程也很重要。第三，我们的比较研究将提供一个机会来了解病毒RNA元件如何适应和进化，这很重要，因为病毒进化可以影响病毒的致病性、耐药性和宿主范围。最后，核糖调控的知识在生物技术中具有潜在的有益应用；例如，通过开发针对和抑制病毒RNA元件活性的新型抗病毒策略，或通过修改其在例如基于病毒的蛋白质表达载体中的活性，从而提高其性能。

RNA viruses represent a serious threat to the health of plants and animals. The goal of our research program is to gain a detailed understanding of the fundamental steps in the reproductive cycle of this type of infectious agent. Our laboratory focuses on the area of "viral riboregulation" – the mechanisms by which viral RNA elements within viral RNA genomes regulate critical steps in the infectious process. Our studies utilize members of the plant virus family Tombusviridae, which are small spherical viruses that contain single-stranded, plus-sensed (i.e. messenger-sensed) RNA genomes and cause diseases in a variety of important crop plants. We focus on the prototype member of this family, Tomato bushy stunt virus (TBSV), which represents an excellent model virus for understanding the infectious process at the molecular level. To determine how viral RNA elements function, we will use different methods, including computational, biochemical, molecular and cellular techniques. The results from these studies of the TBSV RNA genome will allow us to better understand this multifunctional RNA machine and build a comprehensive multi-dimensional model of riboregulation for viral infection. Additionally, we will extend our genomic RNA structure-function analyses to other genera in the family Tombusviridae in order to identify novel viral RNA elements and determine how these structural features diverge and evolve. Understanding viral riboregulation is important for several reasons. First, it represents a fundamental and distinctive type of regulatory strategy used by many viruses, so our results will likely be relevant to other RNA viruses, and possibly cellular mRNAs. Second, our work in this field has helped to promote the novel concept that, in addition to local RNA elements, the overall architecture of viral RNA genomes is also important for controlling viral processes. Third, our comparative studies will provide an opportunity to learn how viral RNA elements adapt and evolve, which is important because virus evolution can affect viral pathogenicity, resistance, and host range. Finally, knowledge of riboregulation has potential beneficial applications in biotechnology; e.g. through the development of novel antiviral strategies that target and inhibit the activity of viral RNA elements or by modifying their activities in, for example, virus-based protein expression vectors, so as to improve their performance.