Innate Biotechnologies LLC, Denver, CO, USA.
Methods Mol Biol. 2020;2128:107-114. doi: 10.1007/978-1-0716-0385-7_8.
Studies performed in humans and animal models have implicated the environment in the etiology of type 1 diabetes (T1D), but the nature and timing of the interactions triggering β cell autoimmunity are poorly understood. Virus infections have been postulated to be involved in disease mechanisms, but the underlying mechanisms are not known. It is exceedingly difficult to establish a cause-and-effect relationship between viral infection and diabetes in humans. Thus, we have used the BioBreeding Diabetes-Resistant (BBDR) and the LEW1.WR1 rat models of virus-induced disease to elucidate how virus infection leads to T1D. The immunophenotype of these strains is normal, and spontaneous diabetes does not occur in a specific pathogen-free environment. However, β cell inflammation and diabetes with many similarities to the human disease are induced by infection with the parvovirus Kilham rat virus (KRV). KRV-induced diabetes in the BBDR and LEW1.WR1 rat models is limited to young animals and can be induced in both male and female rats. Thus, these animals provide a powerful experimental tool to identify mechanisms underlying virus-induced T1D development.
在人类和动物模型中进行的研究表明，环境在 1 型糖尿病（T1D）的发病机制中起作用，但触发β细胞自身免疫的相互作用的性质和时间尚不清楚。病毒感染被认为与疾病机制有关，但潜在的机制尚不清楚。要在人类中建立病毒感染与糖尿病之间的因果关系极其困难。因此，我们使用了生物繁殖糖尿病抵抗（BBDR）和 LEW1.WR1 大鼠病毒诱导疾病模型，以阐明病毒感染如何导致 T1D。这些品系的免疫表型正常，在无特定病原体环境中不会发生自发性糖尿病。然而，细小病毒 Kilham 大鼠病毒（KRV）感染会导致 BBDR 和 LEW1.WR1 大鼠的β细胞炎症和类似于人类疾病的糖尿病。在 BBDR 和 LEW1.WR1 大鼠模型中，KRV 诱导的糖尿病仅限于年轻动物，并且可以在雄性和雌性大鼠中诱导。因此，这些动物为识别病毒诱导的 T1D 发展的机制提供了有力的实验工具。
