Acute onset of type I diabetes mellitus after severe echovirus 9 infection: Putative pathogenic pathways

Abstract

Enterovirus infections have been implicated in the development of type 1 diabetes mellitus. They may cause β cell destruction either by cytolytic infection in the pancreas or indirectly by contributing to autoimmune reactivity. We sought evidence for these 2 mechanisms in a case of acute-onset diabetes mellitus that occurred during severe echovirus 9 infection. The virus was isolated and administered to cultured human β cells. No viral proliferation was observed, and no β cell death was induced, while parallel exposure to Coxsackie B virus serotype 3 resulted in viral proliferation and massive β cell death. Although the viral protein 2C exhibited a sequence similar to that of the β cell autoantigen glutamic acid decarboxylase (GAD65), no cross-reactive T cell responses were detected. The patient did not develop antibodies to GAD65 either. Absence of evidence for direct cytolytic action or an indirect effect through molecular mimicry with GAD65 in the present case raises the possibility of another indirect pathway through which enteroviruses can cause diabetes mellitus.