Viruses as a triggering factor of type 1 diabetes and genetic markers related to the susceptibility to the virus-associated diabetes

Abstract

Type 1 diabetes results from the destruction of insulin-producing pancreatic β cells. Genetic and environmental factors are implicated in the β cell destruction. As environmental factors affecting the induction of type 1 diabetes, diabetogenic viruses, chemicals, toxins, and diet are likely candidates as either primary injurious agents of β cells or triggering agents for the induction of autoimmunity. Regarding viruses as a triggering factor of type 1 diabetes, there are at least two different pathogenic mechanisms in virus-induced diabetes: cytolytic infection of β cells, leading to their destruction, and triggering of autoimmunity, leading to the autoimmune-mediated destruction of β cells. Since there is no correlation between the induction of antibodies to Coxsackie B viruses and the presence of islet cell autoantibodies in patients with type 1 diabetes, the induction of diabetes by Coxsackie B viruses may be due to cytolytic infection of β cells rather than an autoimmune response. In contrast, rubella virus and cytomegalovirus (CMV) do appear to be somehow associated with autoimmune type 1 diabetes since there is a strong correlation between the presence of islet cell autoantibodies and persistent infections. Regarding genetic factors, there are distinct markers related to the susceptibility to Coxsackie B4 virusassociated type 1 diabetes and CMV-associated type 1 diabetes. Four specific DNA restriction endonuclease fragments ( BamHI-DQ-β 6.6, TaqI-DR-β 4.3, TaqI-DR-β 2.5 and TaqI-DR-β 1.5 kb) are related to the susceptibility to Coxsackie B4 virus-associated type 1 diabetes while six specific DNA restriction endonuclease