Coxsackievirus B4 heterogeneity: effect of passage on neutralization and mortality.

We have compared two CB4 isolates for virulence, tissue tropism, and antigenic drift using monoclonal antibodies. Both isolates replicated in C57B1/6 and Balb/c mice. The human isolate Edwards, recovered from a fatal case of encephalohepatomyocarditis, produced lethal infection in adult animals. Lethal infections were associated with high viral titers in visceral organs but not with the presence of specific neutralizing epitopes. Virulence seemed stable upon passage, and also the avirulent JVB isolate retained its phenotype. Mock infection and recovery experiments demonstrated the stability of these characteristics. Neither the tissue from which the virus was isolated nor the cell line used in isolation significantly reduced virulence. However, antigenic variation among isolates was abundant. Thus, the set of monoclonal antibodies employed here may not be appropriate positive markers for virulence. This study suggests that CB4 virulence is stable upon extended in vitro passage and limited in vivo passage and that isolation site and method may not select for or against virulence. It is therefore possible that laboratory adapted strains of CB4, although antigenically different from freshly isolated specimens, may still retain these properties responsible for virulence present in low passage isolates and may be, with regard to virulence, very similar to freshly isolated specimens.