Factors affecting the infection of the D variant of encephalomyocarditis virus in the B cells of C57BL/6J mice

Summary The D variant of encephalomyocarditis viras is capable of infecting most inbred strains of mice. However, only certain strains are susceptible to the diabetogenic effect of this viras. In order to understand why some inbred strains do not become diabetic, the pathogenesis of infection was studied in diabetes-resistant C57BL/6J mice. It was the purpose of the investigation to ascertain whether specific host defense factors might play a crucial role in the mechanism of resistance. To determine whether perturbations of the immune response would alter the resistance of these animals, mice were treated with a high dose (1.15 mmol/kg body weight) of the T- and B-cell toxin cyclophosphamide prior to infection with the D variant. This treatment did not induce overt diabetes or glucose intolerance in the mice tested 7 days after infection. Based on this finding, it appeared likely that resistance to the D variant is conveyed by some factor other than cell-mediated immunity. A likely candidate to control this viral infection is the interferon system. To investigate this possibility, C57BL/6J mice were infected with the D variant and the concentrations of serum interferon titred at various intervals thereafter. In contrast to previous reports with diabetes susceptible mice, C57BL/6J mice were found to generate a substantial interferon response against this variant, with peak levels found in the serum at 24 h following infection. Additional studies were performed in which mice were treated with antibody to mouse interferon alpha/beta at the time of infection and again 3 days after infection with the D variant. Sixty percent of the animals treated in this manner became glucose intolerant. The results of these studies indicate that the interferon system is a critical determinant of resistance to the diabetogenic effect of the D variant in C57BL/6J mice.