Virus-induced diabetes mellitus. XVIII. Inhibition by a nondiabetogenic variant of encephalomyocarditis virus.
Plaque purification of the M variant of encephalomyocarditis (EMC) virus resulted in the isolation of two stable variants: one diabetogenic and designated D and the other nondiabetogenic and designated B. When the D variant was inoculated into SJL/J male mice, hypoinsulinemia and hyperglycemia developed in > 90% of the animals. In contrast, none of the mice inoculated with the B variant developed diabetes. Histologic examination of pancreata from mice infected with the D variant revealed insulitis and necrosis of beta cells, whereas islets from mice infected with the B variant showed little, if any, change. When islets were assayed for infectious virus, approximately 10 times more virus was recovered from animals inoculated with the D as compared with the B variant. Moreover, approximately 60% of islet cells from mice infected with the D variant contained viral antigens when stained with fluorescein-labeled anti-EMC virus antibody, whereas < 5% of islet cells from animals infected with the B variant contained viral antigens. Co-infection experiments showed that the induction of diabetes by the D variant was inhibited by the B variant. When the B and D variants were mixed together at B:D ratios of 1, 9, and 99, diabetes developed in 60, 11, and 0% of the mice, respectively. Tissue-culture experiments revealed that the B variant induced considerably more interferon than the D variant, and studies in animals showed that interferon appeared earlier and in greater amounts in the circulation of mice infected with the B as compared with the D variant. These studies suggest that the induction of interferon by the B variant is, at least in part, responsible for the inhibition of diabetes by the D variant.
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000382:microbiology*; D004686:Encephalomyocarditis virus / Q000235:genetics* / Q000472:pathogenicity; D014644:Genetic Variation; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D010179:Pancreas / Q000382:microbiology; D014774:Virulence
D000956:Antigens, Viral; D001786:Blood Glucose; D007328:Insulin