VIRAL DIABETES: VIRUS DIABETOGENICITY AND HOST SUSCEPTIBILITY

Abstract

Diabetes mellitus (DM) is on the rise worldwide, and is associated with improvement in socioeconomic conditions, increasing wealth, high caloric and fat intake, and reduced physical activity. Accumulating evidence also suggests a causal/triggering link with environmental factors, such as toxins and viruses. A variety of viral infections have been associated with the development of diabetes. There might be no ‘diabetes virus’, but there might be a variety of ‘diabetogenic viruses’ that contribute to diabetes in people who are particularly susceptible due to genetic or physiologic conditions. Increasing evidence is showing that human enteroviruses (EVs) are prominent among possible causal candidates for type 1 diabetes mellitus (T1D). However, evidence for diabetogenicity of viruses is still missing. For a pathogen, causality should fulfill the etiologic criteria known as ‘modified Koch’s postulates’. Recently, we presented evidence that mutations of Tyk2 gene are responsible for diabetes susceptibility of mice infected with the diabetogenic D strain of encephalomyocarditis virus (EMC-D). Observations have been extended to identify the human polymorphism of TYK2 gene associated with increased risk for virus-induced diabetes in humans. An update is given on the possible diabetogenic role of EVs with reference to experimental work in animals and to human studies (viral serology, pancreas histopathology, virus detection in blood and in tissues of diabetic patients). For the identification of a diabetogenic virus, the development of a sensitive experimental model is imperative. In vivo assay systems should include an animal model appropriately simulating a susceptible human and carrying susceptibility genes or factors. This work summarizes current knowledge on virus-induced diabetes together with evidence from experimental models, susceptibility genes in mice, candidate diabetogenic viruses and susceptibility genes in humans. Perspectives on the identification of diabetogenic viruses - which may possibly lead to innovative strategies for the cure or prevention of diabetes – are also presented.