Venezuelan Encephalitis Virus–induced Alterations in Carbohydrate Metabolism in Genetically Diabetic Mice

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We previously reported in this journal that the TC-83-vaccine strain of Venezuelan encephalitis (VE) virus results in a sustained diminution of glucose-stimulated insulin release in golden Syrian hamsters, persisting as long as 90 days after viral infection. This study was designed to examine the metabolic and pathologic consequences of TC-83 VE virus infection in C57 BL/Ks mice (+/+) and in genetic variants of this strain homozygous (db/db) and heterozygous (db/+) for the diabetic gene, db. Five-week-old mice of each genetic variant were inoculated subcutaneously, in groups of 18, with 100,000 plaque-forming units (PFU) of TC-83 that had not been passaged in chick embryo cells or with diluent (control mice). The clinical course in all three groups of mice following VE inoculation was mild, with a 5 to 10% mortality. By light microscopy, control +/+, TC-83 VE-infected +/+, control db/+, and TC-83 VE-infected db/+ pancreases manifested no appreciable difference in morphology. Uninfected db/db mice showed typical changes, including a definite decrease in the number of aldehyde fuchsin-staining granules in beta cells. TC-83 VE-infected db/db mice exhibited a profound decrease in pancreatic beta cell granulation on aldehyde fuchsin staining. After TC-83 VE inoculation, the most striking alterations in carbohydrate metabolism occurred in db/db mice, which showed further worsening of glucose tolerance 120 min after intraperitoneal glucose as well as significantly decreased basal and glucose-stimulated immunoreactive insulin (IRI) levels. After TC-83 VE infection, pancreatic IRI content was not decreased in +/+ or db/+ mice but was virtually absent in db/db mice. The data support the ability of TC-83 VE to inhibit glucose-stimulated IRI release in three genetic variants of C57 BL/Ks mice. In addition, this model demonstrates the heightened susceptibility of the remaining diabetic beta cells in the db/db mice to subsequent infection with a pancreatropic virus.