Grant: Discovery Grants Program - Individual

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.