Virus-induced diabetes mellitus: mengovirus infects pancreatic beta cells in strains of mice resistant to the diabetogenic effect of encephalomyocarditis virus

Abstract

In mice, mengovirus produces a fatal encephalitis. Plaque purification of the virus resulted in the isolation of a clone (Mengo-2T), which in addition to encephalitis caused diabetes. Microscopic examination of pancreases from infected mice revealed necrosis in the islets of Langerhans and infiltration of inflammatory cells. By immunofluorescence viral antigens were found in the islets, and radioimmunoassays demonstrated a substantial decrease in pancreatic immunoreactive insulin. Studies on susceptibility among inbred strains of mice showed that whereas the D variant of encephalomyocarditis virus caused diabetes only in SJL/J mice, Mengo-2T caused diabetes in strains of mice resistant to encephalomyocarditis-induced diabetes (i.e., CBA/J, C3H/HeJ, CE/J, AKR/J, C57BL/6J). The ability of Mengo-2T to induce diabetes in encephalomyocarditis-resistant mice was found to be due to the greater capacity of Mengo-2T as compared to the D variant of encephalomyocarditis virus to replicate in and destroy the islets of these animals. Although Mengo-2T and the D variant of encephalomyocarditis virus are antigenically indistinguishable by hyperimmune sera, these studies show that these viruses have different host ranges and tissue tropisms.