We use dsRNA viruses from the families Reoviridae (primarily orthoreoviruses and rotaviruses), Partitiviridae, and Totiviridae to study fundamental aspects of structure-function relationships in virus particles, virus particle assembly, virus-cell interactions, and viral pathogenesis. Areas of current focus include the following.

Virus entry into cells. We are interested to define the biochemical and biophysical mechanisms by which nonenveloped viruses penetrate the cellular membrane barrier during entry. Since these viruses lack a lipid envelope that they can fuse with the cell’s, mechanisms distinct from fusion are required.

Synthesis, processing, and transport of viral RNA. The genome-enclosing capsid particle of the dsRNA viruses represents a biochemically defined system for RNA-dependent RNA transcription, RNA 5´ capping, and mRNA transport. Though much simpler than the related machinery of cells, this system is providing new insights into the structural and dynamic aspects of these basic processes.

irus assembly inside cells. The volume of a cell is large compared to the small portion used by most viruses for their assembly. Moreover, the cell is highly compartmentalized with regard to different functions that viruses may need. We are interested to define specific elements of cellular organization that viruses exploit to benefit their own replication. Particular focus is on the content and organization of the cytoplasmic “factories” in which viral replication and assembly occur.

Viral pathogenesis. Orthoreoviruses and rotaviruses are mucosal pathogens that provide powerful models for studies of virus-host interactions and viral pathogenesis. Viral interactions with the mucosal epithelium and the mucosal immune system may be especially useful for the design of more successful mucosal vaccines.

Different approaches are used in our lab as the questions dictate, but biochemical, molecular, and genetic approaches predominate. Collaborations with structural and cellular biologists are embraced to extend our characterizations to higher levels of mechanistic resolution.