Regulation of Viral RNA Replication

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Viruses must produce their gene products in the proper amounts and with the appropriate timing. Failure to do so can activate innate defense responses from the host. Perhaps in response to the challenges from the host, viruses have adapted a number of regulatory mechanisms, many of which work either synergistically or as molecular switches to shut down other processes. This project will study how regulatory processes are integrated during the infection of a model plus-strand RNA virus named Brome Mosaic Virus (BMV). The three objectives of the project will: 1) examine the role of two cellular proteins that compete for binding of the viral RNA motif that regulates minus-strand RNA synthesis, 2) determine how the BMV capsid protein can regulate the transition from RNA synthesis to RNA encapsidation, and 3) characterize also how a key BMV replication protein plays a dual role in translation and the assembly of the viral replication enzyme complex. The focus of this work represents a more integrative approach to studies of the viral infection process the anticipated result should be informative for all RNA viruses. In addition, the anticipated results will contribute to our understanding of gene regulation, protein-RNA interactions, and crosstalk between basic processes. This research will also provide a forum to train students as problem solvers. Students will be trained to use interdisciplinary approaches to study viral pathogens. Over two dozen students, ranging from high schoolers to postdocs, including underrepresented inorities, have been trained on this project with prior support. The next phase of this research will continue this training tradition.