Molecular study of reovirus outer capsid proteins: fundamental aspects and applications.

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Mammalian reoviruses have played an important role in our understanding of important biological mechanisms: virus entry, synthesis of nucleic acids and proteins, virus evolution, and many more. In addition to their interest as fundamental research tools, possible applications for reoviruses are envisaged. Some viruses, such as reoviruses, can now become our "allies" rather than just enemies to fight. The ability of reoviruses to infect humans and a large range of animal species suggests the possibility of developing novel applications for these viruses. Furthermore, it is now clearly established that reoviruses preferentially infect and kill cancer cells; they are thus attractive candidates for the development of "virotherapy" anticancer treatments. My laboratory has been actively involved in the study of various aspects of the biology of reoviruses, and this for the last 18 years. Molecular biology, biochemistry, and classical genetics approaches, have been especially useful to dissect the structure and function of viral proteins. It is now proposed to pursue these studies to develop a better fundamental understanding of the viral replication cycle, an understanding that is essential for the development of practical applications for these viruses. Three different proteins will be studied: these are involved in virus entry, discrimination between normal and cancer cells, and virus assembly. We will take advantage of the availability of viral gene sequences and mutants to determine the role of the various proteins and to further modify them using genetic engineering tools. We believe that these studies should significantly contribute to our long-term objectives aimed at developing and optimizing practical applications for reoviruses in animal and human biology.