BioMedical Research Models, Worcester, Massachusetts, USA.
Diabetes. 2010 Jan;59(1):110-8. doi: 10.2337/db09-0255. Epub 2009 Sep 30.
The contribution of antecedent viral infection to the development of type 1 diabetes in humans is controversial. Using a newer rat model of the disease, we sought to 1) identify viruses capable of modulating diabetes penetrance, 2) identify conditions that increase or decrease the diabetogenicity of infection, and 3) determine whether maternal immunization would prevent diabetes.
About 2% of LEW*1WR1 rats develop spontaneous autoimmune diabetes, but disease penetrance is much higher if weanling rats are exposed to environmental perturbants including Kilham rat virus (KRV). We compared KRV with other viruses for diabetogenic activity.
Both KRV and rat cytomegalovirus (RCMV) induced diabetes in up to 60% of LEW1WR1 rats, whereas H-1, vaccinia, and Coxsackie B4 viruses did not. Simultaneous inoculation of KRV and RCMV induced diabetes in 100% of animals. Pretreatment of rats with an activator of innate immunity increased the diabetogenicity of KRV but not RCMV and was associated with a moderate rate of diabetes after Coxsackie B4 and vaccinia virus infection. Inoculation of LEW1WR1 dams with both KRV and RCMV prior to pregnancy protected weanling progeny from virus-induced diabetes in a virus-specific manner.
Exposure to viruses can affect the penetrance of autoimmune diabetes in genetically susceptible animals. The diabetogenicity of infection is virus specific and is modified by immunomodulation prior to inoculation. Maternal immunization protects weanlings from virus-induced diabetes, suggesting that modification of immune responses to infection could provide a means of preventing islet autoimmunity.
关于先天病毒感染对人类 1 型糖尿病发展的作用仍存在争议。利用一种新的糖尿病大鼠模型，我们试图：1）鉴定能调节糖尿病易感性的病毒；2）鉴定增加或降低感染致糖尿病性的条件；3）确定母体免疫接种是否能预防糖尿病。
大约 2%的 LEW*1WR1 大鼠会发生自发性自身免疫性糖尿病，但如果新生大鼠接触环境应激原，如 Kilham 大鼠病毒（KRV），则疾病的易感性会大大增加。我们比较了 KRV 与其他病毒的致糖尿病活性。
KRV 和大鼠巨细胞病毒（RCMV）均可使高达 60%的 LEW1WR1 大鼠发生糖尿病，而 H-1、牛痘和柯萨奇 B4 病毒则不能。同时接种 KRV 和 RCMV 可使 100%的动物发生糖尿病。用先天免疫激活剂预处理大鼠可增加 KRV 的致糖尿病性，但不增加 RCMV 的致糖尿病性，并且与柯萨奇 B4 和牛痘病毒感染后中等比例的糖尿病相关。在妊娠前给 LEW1WR1 母鼠接种 KRV 和 RCMV 可特异性地保护新生仔鼠免受病毒诱导的糖尿病。
病毒暴露可影响遗传易感动物自身免疫性糖尿病的易感性。感染的致糖尿病性具有病毒特异性，并可通过接种前的免疫调节来修饰。母体免疫接种可保护新生仔鼠免受病毒诱导的糖尿病，这表明修饰对感染的免疫反应可能是预防胰岛自身免疫的一种手段。
