Heterogeneity of a human isolate of Coxsackie B4: biological differences

Evidence is presented to demonstrate existence of virion heterogeneity within the human isolate, Edwards, of Coxsackievirus B4 (CB4-Edw). Three virion types (E1, E2 and E3) were cloned by repeated plaque purification of CB4-Edw and then all were compared relative to their effects on the pancreas of mice during acute infection. Seventy-two hours post-infection blood glucose, plasma amylase and insulin levels were monitored in mice of the SWR/J strain (previously classified susceptible to other diabetogenic picornaviruses), and the C57B1/6J strain (resistant). While all the viruses caused pancreatitis none of the animals infected with any of the clones showed as dramatic an increase in plasma amylase levels (four- vs 20-fold) as is characteristic of C57B1/6J mice inoculated with the original CB4 Edw virus. Greatest differences were expressed between the clones and CB4-Edw while less substantiative differences were found among the clones. For instance, clone E1 depressed blood glucose levels in C57B1/6J mice without affecting insulin levels. Likewise, the clone E2 depressed blood glucose levels without affecting insulin levels but only in SWR/J animals. This study demonstrates the heterogeneity of a human isolate of CB4. The subpopulation of virions contained within this isolate differ in the biological responses they elicit, specifically with regard to diabetogenic potential.