Analysis of the role of rotavirus infection in development of type 1 diabetes

我们早期对有1型糖尿病家族史的儿童的研究表明，感染一种常见的病毒，轮状病毒，可能是导致他们进展为糖尿病的一个因素。轮状病毒是幼儿腹泻、呕吐和脱水的最常见原因，人们认为轮状病毒感染通常局限于肠道。为了了解轮状病毒感染是如何促进糖尿病的，我的团队开发了一种小鼠模型。使用小鼠进行这些研究使我们能够控制感染并完全分析感染结果，这在人类身上是无法做到的。一种很可能在出生后6个月内患上1型糖尿病的老鼠，通过口腔感染轮状病毒。我们已经证明，这些老鼠比没有注射病毒的同类型老鼠患糖尿病的速度快了7周。在这个项目中，我们将确定小鼠年龄、病毒株、感染次数以及肠道或胰腺中病毒生长水平对病毒诱导的糖尿病加速的影响。轮状病毒感染的治疗和轮状病毒疫苗预防这种加速糖尿病的能力也将得到检验。我们预计会发现轮状病毒在胰腺中生长，这种病毒的生长是糖尿病加速的必要条件，预防轮状病毒感染也将防止糖尿病的快速发病。这个模型可能被证明适合于测试针对轮状病毒和1型糖尿病的新药和疫苗的有效性和安全性。我们的研究对于确定轮状病毒感染在1型糖尿病发展中的重要性至关重要。

Our earlier studies in children with a family history of type 1 diabetes have shown that infection with a common virus, rotavirus, may be one factor contributing to their progression to diabetes. Rotavirus is the most common cause of diarrhoea, vomiting and dehydration in young children, and it was thought that rotavirus infection is usually confined to the intestine. To understand how rotavirus infection might promote diabetes, my group has developed a mouse model. Using mice for these studies allows us to control infection and completely analyse the results of infection, which we cannot do in humans. A type of mouse that is very likely to develop type 1 diabetes in its first 6 months of life is infected by mouth with rotavirus. We have shown that these mice develop diabetes 7 weeks faster than the same type of mice that are not given virus. In this project, we will determine the effects of mouse age, virus strain, the number of times infection occurs, and levels of virus growth in the intestine or pancreas on virus-induced diabetes acceleration. The ability of treatments for rotavirus infection, and vaccination against rotavirus, to block this accelerated diabetes also will be tested. We expect that rotavirus will be found growing in the pancreas, that virus growth is necessary for diabetes acceleration, and that prevention of rotavirus infection will also prevent the rapid diabetes onset. This model could prove to be suitable for testing the effectiveness and safety of new drugs and vaccines against both rotavirus and type 1 diabetes. Our studies will be crucial in determining the importance of rotavirus infection in the development of type 1 diabetes.