Persistent virus infection associated with chemical manifestations of diabetes. II. Role of viral strain, environmental insult, and host genetics.
Abnormal glucose metabolism (hyperglycemia and/or aberrant glucose tolerance test) occurred over the life-times of mice persistently infected with lymphocytic choriomeningitis virus (LCMV). Persistent infection could be initiated in both newborn and adult mice. For newborns, inoculation with any of several strains of LCMV (Armstrong, E350, Pasteur, Traub or WE) caused continuous infection, but such infection of adults required a selected lymphotropic variant of LCMV Armstrong (Clone 13). Throughout these animals' lives, viral materials (nucleic acid sequences and proteins) accumulated in multiple tissues, including the beta-cells of the islets of Langerhans; infectious virus was present in blood and tissues, and the LCMV-specific H-2 restricted CTL response was poor. Adult mice that had been inoculated with virus as newborns displayed neither histopathologic injury nor infiltrates of mononuclear cells in the islets of Langerhans despite moderate viral replication in beta-cells. In contrast, mice inoculated as adults with Clone 13 LCMV consistently developed inflammatory infiltrates in perivascular spaces of the islets of Langerhans, and their beta-cells expressed LCMV antigens. Addition of a subdiabetogenic dose of streptozotocin, a specific beta-cell toxin, magnified the virus-induced abnormality in glucose metabolism. This indicated a potentiating role between persistent virus infection initiated at birth or in adulthood and an environmental factor in causing abnormalities in glucose metabolism.
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000209:etiology / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006943:Hyperglycemia / Q000139:chemically induced / Q000209:etiology; D007515:Islets of Langerhans / Q000382:microbiology; D008216:Lymphocytic Choriomeningitis / Q000150:complications / Q000378:metabolism*; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics* / Q000502:physiology; D051379:Mice / Q000235:genetics*; D008815:Mice, Inbred Strains; D009765:Obesity / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013311:Streptozocin / Q000008:administration & dosage; D013997:Time Factors
D013311:Streptozocin; D005947:Glucose