Type 1 Diabetes in Swedish Bank Voles (Clethrionomys glareolus): Signs of Disease in Both Colonized and Wild Cyclic Populations at Peak Density

Abstract

Colonized bank voles (Clethrionomys glareolus) originating from Sweden developed type 1 diabetes. Animals became polydipsic, glucosuric, and hyperglycemic and gradually developed a lethal ketoacidosis. Pancreas in animals with end-stage disease showed total destruction of islet cells. Interestingly, also a high proportion of wild bank voles in cyclic populations that were trapped at (or close to) the cyclic population density peak frequently showed high blood glucose levels and pathological glucose tolerance test. Extensive islet destruction was not seen in wild bank voles at the time of capture, but did develop in some of the animals over a time period of two months. Diabetes in both colonized and wild bank voles was associated with Ljungan virus (LV). LV could be isolated from the pancreas of diabetic bank voles and antigen detected at the site of tissue damage by immunohistochemistry. In addition, picornavirus-like particles were visualized in the islets of diabetic voles using thin-section transmission electron microscopy.

Ljungan Virus Detected in Bank Voles (Myodes glareolus) and Yellow-Necked Mice (Apodemus flavicollis) from Northern Italy

“…This pathogen, subsequently named the Ljungan virus (LV), has been identified in wild voles in Denmark and the United States, as well as in lemmings and inbred laboratory rats (Johansson et al, 2003;Niklasson et al, 2003aNiklasson et al, , 2006aNiklasson et al, , 2007aSamsioe et al, 2006). In addition, LV has been shown to induce type 2-like diabetes, uterine resorptions, malformations, and neonatal death in CD-1 laboratory house mice (Niklasson et al, 2006b;Samsioe et al, 2006).…”

“…In 1998, Niklasson and colleagues isolated a picornavirus in natural populations of the bank vole (Myodes glareolus) in northern Sweden that causes clinically recognizable type 1 diabetes-like symptoms in this species (Niklasson et al, 1998(Niklasson et al, , 1999(Niklasson et al, , 2003a. This pathogen, subsequently named the Ljungan virus (LV), has been identified in wild voles in Denmark and the United States, as well as in lemmings and inbred laboratory rats (Johansson et al, 2003;Niklasson et al, 2003aNiklasson et al, , 2006aNiklasson et al, , 2007aSamsioe et al, 2006).…”

“…In addition, LV has been shown to induce type 2-like diabetes, uterine resorptions, malformations, and neonatal death in CD-1 laboratory house mice (Niklasson et al, 2006b;Samsioe et al, 2006). It has also been noted that the manifestation of various symptoms in LV-infected animals increases with stress (Freimanis et al, 2003;Niklasson et al, 2003aNiklasson et al, , b, 2006bSamsioe et al, 2006). Intriguingly, in Sweden it has been shown that the incidence of type 1 diabetes, GuillainBarré syndrome, and myocarditis in the human population is correlated with rodent population cycles (Niklasson et al, 1998), and children newly diagnosed with type 1 diabetes have significantly increased levels of LV antibodies compared to controls (Niklasson et al, 2003a).…”

The BioBreeding rat diabetes model is infected with Ljungan virus

“…This led us to hypothesise that the bank vole is the reservoir and/ or vector of an infectious agent causing this disease in a predisposed population of humans. The hypothesis was supported by the observation that wild-trapped bank voles developed symptoms of diabetes in captivity [2]. A novel picornavirus, Ljungan virus (LV), has been isolated from diabetic bank voles in Sweden.…”

“…A novel picornavirus, Ljungan virus (LV), has been isolated from diabetic bank voles in Sweden. Furthermore, viral antigen and picorna viral-like particles were detected by immunohistochemistry (IHC) and electron microscopy in affected pancreatic beta cells [2,3]. Analysis of new and stored samples have shown that LV is also present in wild voles in Denmark and the USA [4].…”