Packaging and Structure of Viral Genomes

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DESCRIPTION (provided by applicant): One of the critical steps in the life cycle of a virus is the packaging of the genome. This research is aimed at understanding the structural, kinetic and thermodynamic aspects of viral packaging in two simple, but very different, systems. Lambdoid bacteriophage use an ATP-driven motor to insert a double-stranded DNA (ds-DNA) genome into a preformed capsid. Nodaviruses assemble the protein capsid around a genome containing two single-stranded RNAs through an orchestrated series of protein-RNA and protein-protein binding events. We will use a variety of tools to develop a series of increasingly detailed three-dimensional molecular models for bacteriophage P4; and for two RNA viruses, satellite tobacco mosaic virus (STMV) and pariacoto virus (PaV). PaV is a well-characterized member of the Nodaviridae family. This research is aimed at rationalizing a wide variety of experimental data, and at developing hypotheses that will motivate future experimental work. The work on ds-DNA bacteriophage is motivated, in part, by the hypothesis that this system is ideal for the development of tools for the more accurate treatment of electrostatic effects, which is critical for further advances in our understanding of structural and thermodynamic issues in nucleic acids. The work on STMV and PaV will test the hypothesis that RNA selection in packaging is not driven by the recognition of a particular RNA sequence or small local structural motif, but by the viral RNA's ability to adopt secondary structures compatible with constraints imposed by viral symmetry.