Grant: Discovery Grants Program - Individual

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.