Reverse genetics study of mammalian reovirus proteins: fundamental studies and possible applications

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Mammalian reovirus has played an important role in our understanding of important biological mechanisms: virus entry, synthesis of nucleic acids and proteins, virus evolution, and much more. In addition to its interest as a fundamental research tool, possible applications are envisaged. Some viruses, such as reovirus, could become our allies rather than just enemies to fight. The ability of reovirus to infect humans and a large range of animal species suggests the possibility of developing novel applications. For example, it is now well established that reovirus preferentially infects and kills cancer cells; it is thus an attractive candidate for "virotherapy" against cancer. In the last 20 years or so, members of the laboratory have been very active in the study of various aspects of reovirus replication. Molecular biology, biochemistry, and classical genetics approaches, have been especially useful to dissect the structure and function of many viral proteins. It is proposed to pursue this work in order to develop a better understanding of viral replication and its effects on infected cells, an aspect judged essential for the future development of therapeutic applications. Since 2007, a novel method known as "reverse genetics" allows introduction of various changes to the reovirus genome. It becomes relatively easy to produce various viral mutants, relying not only to random mutations but using genetic engineering and "site-directed" mutagenesis. This is a major progress to study aspects of viral replication that could not be studied otherwise. Three different proteins will be studied: these play different poorly known roles in virus entry, ability to infect different cells, replicate in and kill these cells. These studies will contribute to long-term objectives aimed at developing and optimizing reovirus' applications in animal and human biology.