Encephalomyocarditis virus-induced diabetes mellitus in mice: model of viral pathogenesis

Abstract

Encephalomyocarditis (EMC) virus induction of diabetes mellitus in mice has proven to be an excellent experimental model for the pathogenesis of viral disease. In SJL and DBA/2 mice, diabetes results exclusively from the infection and damage of beta cells by the virus. In addition, in BALB/cBy mice subclinical beta cell damage caused by the virus is followed by autoimmune beta cell destruction, which results in hyperglycemia. Studies of two closely related plaque variants (EMC-D and EMC-B) selected from the M strain of EMC virus revealed differences in the interferon response associated with viral infection. The EMC-D variant causes diabetes in infected SJL mice by direct beta cell destruction. Infection with EMC-B does not cause diabetes and interferes with the production of diabetes by EMC-D due to the greater ability of EMC-B than of EMC-D to induce interferon in mice. Circulating interferon has a greater effect on inhibition of viral replication because local interferon production is amplified in interferon-primed cells infected with EMC-B. These properties are determined by the interferon-inducing particle (Ifp+) phenotype of EMC-B and the Ifp- phenotype of EMC-D.