A new look at viruses in type 1 diabetes

Abstract

Type 1 diabetes (T1D) results from the destruction of pancreatic beta cells. Genetic factors are believed to be a major component for the development of T1D, but the concordance rate for the development of diabetes in identical twins is only about 40%, suggesting that nongenetic factors play an important role in the expression of the disease. Viruses are one environmental factor that is implicated in the pathogenesis of T1D. To date, 14 different viruses have been reported to be associated with the development of T1D in humans and animal models. Viruses may be involved in the pathogenesis of T1D in at least two distinct ways: by inducing beta cell-specific autoimmunity, with or without infection of the beta cells, [e.g. Kilham rat virus (KRV)] and by cytolytic infection and destruction of the beta cells (e.g. encephalomyocarditis virus in mice). With respect to virus-mediated autoimmunity, retrovirus, reovirus, KRV, bovine viral diarrhoea-mucosal disease virus, mumps virus, rubella virus, cytomegalovirus and Epstein-Barr virus (EBV) are discussed. With respect to the destruction of beta cells by cytolytic infection, encephalomyocarditis virus, mengovirus and Coxsackie B viruses are discussed. In addition, a review of transgenic animal models for virus-induced autoimmune diabetes is included, particularly with regard to lymphocytic choriomeningitis virus, influenza viral proteins and the Epstein-Barr viral receptor. Finally, the prevention of autoimmune diabetes by infection of viruses such as lymphocytic choriomeningitis virus is discussed.

The Role of Toll-Like Receptor Pathways in the Mechanism of Type 1 Diabetes

“…Environmental factors and viral infections in particular are implicated in the mechanism leading to diabetes [71][72][73]. Several lines of evidence support this possibility.…”

Toll-like Receptor 3 and STAT-1 Contribute to Double-stranded RNA+ Interferon-γ-induced Apoptosis in Primary Pancreatic β-Cells

“…Thus, viruses may directly infect and destroy pancreatic ␤-cells or they may trigger (or contribute to) ␤-cellspecific autoimmunity with or without direct ␤-cell infection; viruses may also alter some mechanisms of peripheral tolerance (7)(8)(9). For example, mouse infection with a high titer of the D variant of the encephalomyocarditis virus causes ␤-cell destruction and diabetes as a result of viral replication within ␤-cells, whereas mouse infection with a low titer of encephalomyocarditis D virus leads to diabetes as a chronic process, induced by the destruction of ␤-cells by macrophage-produced soluble mediators such as IL-1␤, tumor necrosis factor-␣/␤, and NO (10).…”

Helicobacter pylori in Autoimmune Pancreatitis and Pancreatic Carcinoma

“…As to the pancreas, several viral infections are known [4], and associations with diabetes mellitus have been described [5,6]. On the other hand, Helicobacter pylori has gained considerable interest for a variety of reasons.…”