Reoviruses are dsRNA viruses of the Reoviridae family, which includes human (rotavirus) and veterinary (blue tongue disease) pathogens. The mu2 protein, an inner capsid component of reovirus, is suggested to be a regulator of viral cytopathology. It was discovered that mu2 localizes to the nucleus/nucleolus, has transport signals and interacts with host nuclear import/export receptors. To further explore mu2 structure and function, mu2 nuclear/nucleolar transport will be characterized using a reverse genetics system to determine the functional relevance for mu2 localization on reovirus life cycle and pathogenesis. Functionally relevant mammalian protein binding partners for mu2 will be identified through protein binding studies through a yeast two-hybrid genetic interaction screen using mu2 as bait and a mammalian cDNA library as prey. Cell biological approaches comparing WT versus mutant mu2 proteins will be used to map structural-functional domains of mu2 and determine how mu2 alters host nuclear function. Characterization of mu2 will give a better understanding of reovirus, be applicable to other cytoplasmically replicating RNA viruses, and possibly lead to the development of better anti-viral therapies.