A positive correlation was found between genetic predisposition to diabetes in the mouse and susceptibility to group B Coxsackie virus in this host. Male mice of the inbred strain C57BL/Ks and the following genetic variants were used; mice homozygous for the autosomal recessive gene for diabetes (db/db), the phenotypically normal heterozygous (db/+), and the normal mice which lacked the diabetic gene (+/+). The mortality response of the +/+ mice to intraperitoneal inoculation with Coxsackie virus B4 differed from the response of the two genetic variants (db/db and db/+) derived from this strain. The db/+ variant was more susceptible to Coxsackie virus B4 than the parental background strain (+/+). The db/db variant was more susceptible than either of the other genotypes. Pathological findings of the pancreas of the three genotypes during the acute stage of infection closely paralleled the genotypically dependent susceptibility of the host.

Adult male mice were made hypercholesterolemic by a diet high in cholesterol, cholic acid, animal fat, and sucrose. After three months on this diet, animals were infected with 5 X 10(9) plaque-forming units of coxsackievirus B5. Control groups consisted of uninfected hypercholesterolemic mice and infected mice maintained on a standard laboratory diet. Infection in the hypercholesterolemic animals was associated with leukopenia, severe fatty metamorphosis and focal necrosis in the liver, cholelithiasis, ileus, cardiomyolysis, and lack of inflammatory response. These mice died within seven to 14 days. Uninfected hypercholesterolemic animals had lesser degrees of fatty liver and cholelithiasis, and all survived. Infected mice maintained on a standard diet also survived. Titers of virus in representative tissues were lower in the hypercholesterolemic than in the normal mice, an indication that replication of virus was not solely responsible for the lethal outcome of the infections. These experiments demonstrate that hypercholesterolemia may alter host defenses against group B coxsackievirus in the mouse.

The ability of different strains of a single virus type to produce different pathogenic expressions is well documented within the picornavirus group. Coxsackievirus, group B, type 4 (CB4) has been associated with viral-induced diabetes in man, but expression of its potential to induce diabetes in experimental animals is variable. Evidence is presented here for one of the primary sources of this variability that could explain resulting contradictory reports offered in support or rejection of its diabetogenic potential. C57B1/6 and SWR mice were infected with the Edwards isolate of CB4 (CB4-Edw) and three of its plaque-purified virion "strains." These were designated Edwards isolate-1 (E1), E2, and E3. CB4-Edw, E1, E2, and E3 were serologically similar by infectivity neutralization tests, had identical plaque morphology, and replicated to a similar level in the pancreas. The most profound difference was the level of virus antigen accumulation in the islet cells as determined by immunoperoxidase localization. CB4-Edw had moderate antigen accumulation in most islet cells of SWR mice but was restricted to only a few specific cells within the periphery islets of C57B1/6 mice. Unlike CB4-Edw all three new isolates accumulated antigen in most islet cells of both mouse strains. Virus isolate (strain) E2 showed the most intense accumulation in islet cells. These observations suggest that the Edwards isolate of CB4, like other human isolates of CB4 virus, probably exists as a heterogeneous population of virion strains. The pathogenic consequences and expression of any diabetogenic potential is, therefore, dependent on virus strain selection. This diversity must be considered when evaluating the pathogenic nature of CB4 viruses in experimental animals and the possible role of the viruses in diabetes of man.

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