Severity of disease induced by a pancreatropic Coxsackie B4 virus correlates with the H-2Kq locus of the major histocompatibility complex.
Coxsackie B viruses are known etiological agents of pancreatic diseases, including diabetes. The pathogenesis of these infections is influenced by both host and viral factors. In this report, we examined whether the outcome of Coxsackie B4 virus infection is dependent on the genes within the major histocompatibility complex (MHC). We generated a pancreatic variant, CB4-V and established an animal model system of pancreatitis with concurrent hypoglycemia in mice. Infection of various B10 H-2 congenic strains of mice revealed that the development of hypoglycemia with accompanying pancreatitis was independent of the MHC haplotype. However, the severity of the disease as monitored by the extent and duration of hypoglycemia and by mortality rate was found to be associated with the H-2 haplotype, specifically the H-2Kq locus. Pancreatic damage induced by CB4-V appeared to be both immune-mediated and viral-mediated. Histological examination of pancreatic tissue from infected B10 H-2 congenic mice revealed an association between acute destruction of the exocrine pancreas and lymphocytic infiltration. This infiltration may correlate with immune-mediated destruction of the infected pancreatic tissue. Since preferential replication of CB4-V was not observed in the most susceptible B10 mouse strain, direct viral destruction may not be the major mechanism of pancreatic injury.
Ramsingh
A
A
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201-0509.
Slack
J
J
Silkworth
J
J
Hixson
A
A
D000818:Animals; D003384:Coxsackievirus Infections / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D029822:Enterovirus B, Human / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D014644:Genetic Variation; D006183:H-2 Antigens / Q000235:genetics*; D007003:Hypoglycemia / Q000209:etiology; D008297:Male; D051379:Mice; D009928:Organ Specificity; D010182:Pancreatic Diseases / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D010195:Pancreatitis / Q000209:etiology; D013045:Species Specificity
D006183:H-2 Antigens