ENTEROVIRUS AND TYPE-1 (INSULIN-DEPENDENT ) DIABETES-MELLITUS

A familial tendency to develop insulin-dependent diabetes mellitus (ID DM) has been described; however, the concordance rate for the developm ent of the disease between monozygotic twins is only about 50%. Enviro nmental factors, including viruses, may be involved in the etiology of the disease. Reports suggested that IDDM may be associated with enter oviral infections. Two studies including ours have detected enterovira l RNA with PCR assays, suggesting current acute or chronic infection, in newly diagnosed IDDM patients. In this review we outline the possib le role of enteroviruses in the pathogenesis of the disease. The role of enteroviruses in chronic diseases have been reported, especially co xsackie B3 virus can be responsible for chronic myocarditis in human. In recent reports, proteins or genome of enterovirus have not been det ected in pancreas from patients with IDDM. However coxsackie B virus h ave been isolated from stools of patients and genome of coxsackie B vi rus have been found in peripheral blood of children and adults at the onset of IDDM. From animal studies it has been shown that coxsackie B4 virus induces hyperglycemia and beta-cell autoimmunity in certains st rains of mice and furthermore viral persistence in the pancreatic beta cells in vitro and can induce long-term changes like inhibition of in sulin synthesis and increased expression of 64 kD autoantigen in beta- cells. Diabetogenic variants of coxsackie B4 virus could arise spontan eously or during the course of infections due to the high rate of muta tion in enteroviruses. Coxsackie B virus sequence data obtained over t he same genomic region from adult patients and from children with IDDM were different. However in each study close similarities between sequ ences pointed to a possible causal relation between genotypic determin ants and the onset of IDDM. The various mechanisms by which enteroviru ses may act to induce IDDM are summarized.