Roles of integrins in rotavirus cell attachment, entry and tropism

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In this project, we aim to discover how rotavirus, the main cause of infantile gastroenteritis, attaches to the surface of cells. Previously, we have shown that rotavirus binds to certain members of the integrin family of proteins on the cell surface. These proteins are intimately involved in cell adhesion, movement, communication and growth. We will continue studies aimed at identifying at the molecular level the requirements for rotavirus interactions with these integrins. It will also be determined whether expression of these integrins on cells from the intestine, kidney, pancreas and immune system is a requirement for the cells to be infected with rotavirus. Previously, we have shown that rotavirus infection may be linked with progression of at-risk children towards development of type I diabetes, a pancreatic autoimmune disease. This means that understanding how the virus interacts with pancreatic and immune cells is of particular importance. The parts of the virus particle which bind to the integrins will be identified, and these will be produced and tested for their ability to block rotavirus infection in cells and in mice. It is likely that rotavirus binds to integrins by a somewhat different mechanism to that used by other viruses and cellular components. If this is so, then in future it should be possible to design drugs which block virus infection without interfering with the normal function of integrins. This work will also provide data useful for design of rotavirus vaccines, and for improved understanding of the disease process.