Roles of integrins in rotavirus cell attachment, entry and tropism

在这个项目中，我们的目标是发现轮状病毒是如何附着在细胞表面的，轮状病毒是婴儿肠胃炎的主要原因。以前，我们已经证明轮状病毒与细胞表面的整合素家族的某些成员结合。这些蛋白质与细胞粘附、运动、通讯和生长密切相关。我们将继续研究，在分子水平上确定轮状病毒与这些整合素相互作用的要求。还将确定这些整合素在肠、肾、胰腺和免疫系统细胞上的表达是否是轮状病毒感染细胞的必要条件。先前，我们已经证明轮状病毒感染可能与高危儿童发展为I型糖尿病（一种胰腺自身免疫性疾病）的进展有关。这意味着了解病毒如何与胰腺和免疫细胞相互作用是特别重要的。病毒颗粒中与整合素结合的部分将被识别出来，这些部分将被生产出来，并测试它们在细胞和小鼠中阻断轮状病毒感染的能力。轮状病毒与整合素结合的机制可能与其他病毒和细胞成分所使用的机制有所不同。如果是这样的话，那么将来就有可能设计出在不干扰整合素正常功能的情况下阻止病毒感染的药物。这项工作还将为轮状病毒疫苗的设计提供有用的数据，并改善对疾病过程的了解。

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.