Viral infections in type 1 diabetes mellitus - why the β cells?

Type1 diabetes mellitus (T1DM) is caused by progressive autoimmune-mediated lossofpancreatic beta-cell mass via apoptosis. The onset of T1DM depends on environmental factors that interact with predisposing genes to induce an autoimmune assault against beta cells. Epidemiological, clinical and pathology studies in humans support viral infection - particularly by enteroviruses (for example, coxsackievirus) - as an environmental trigger for the development of T1DM. Many candidate genes for T1DM, such as MDA5, PTPN2 and TYK2, regulate antiviral responses in both beta cells and the immune system. Cellular permissiveness to viral infection is modulated by innate antiviral responses that vary among different tissues or cell types. Some data indicate that pancreatic islet beta cells trigger a more efficient antiviral response to infection with diabetogenic viruses than do beta cells, and so are able to eradicate viral infections without undergoing apoptosis. This difference could account for the varying ability of islet-cell subtypes to clear viral infections and explain why chronically infected pancreatic beta cells, but not alpha cells, are targeted by an autoimmune response and killed during the development of T1DM. These issues and attempts to target viral infection as a preventive therapy for T1DM are discussed in the present Review.