Pathogenesis of Coxsackievirus B Infections

Regarding the pathogenesis of enteroviral heart disease there has been uncertainty whether viral cytotoxicity or immune-mediated processes are crucial for organ pathology during acute and persistent heart muscle infection. This chapter provides experimental evidence for the decisive role of virus replication in the induction and maintenance of chronic myocardial damage. In addition, the capacity of cellular signal transduction pathways to modulate enterovirus replication as well as coxsackieviruses of group B (CVB) receptor interactions and their role in pathogenesis are discussed. It has been found that in all investigated mouse strains CVB3 is capable of inducing acute myocarditis, which is characterized by virus-induced myocytolysis and reactive formation of interstitial mononuclear infiltrates. Importantly, persistent infection of myocytes was found to be related with morphological changes of the myofibrils. Preferential targets of the enteroviral proteinase 2Apro are proteins involved in the Cap-dependent translation of cellular mRNAs, since enteroviruses employ a Cap-independent mechanism of protein translation. Importantly, recognition of cellular targets by viral proteinases may be preceded by virus-induced modifications of these proteins. As recently suggested for infections with encephalomyocarditis virus, activation of p38/MAPK could be induced by the dsRNA intermediates during enteroviral replication.