Natural history of coxsackievirus B3-induced myocarditis in ACA/Sn mice: viral persistence demonstrated by quantitative in situ hybridization histochemistry

Enteroviruses are considered to be the major aetiological agents of myocarditis in humans. Recent in situ hybridization studies on endomyocardial biopsies and autopsy hearts indicate that enterovirus RNA can be detected (pattern of persistent infection) not only in acute myocarditis (pattern of acute infection), but also in chronic dilated cardiomyopathy. Our experimental studies on murine coxsackievirus B3 myocarditis provided evidence that persistent infection may also occur in mice. Quantitative in situ hybridization and immunohistochemistry as well as electron microscopical in situ hybridization experiments were performed on ACA/SnJ mice 3–30 days after infection. The pattern of acute infection (days 3–9 p.i.) is characterized by rapid progression of myocardial lesions, an increasing number of inflammatory cells and a high number of infected myocytes. Hallmarks of the persistent pattern (days 15–30p.i.) are reduced inflammation, reduced numbers of persistently infected cells and a slow progression of myocardial lesions. Infection is primarily restricted to degenerated, atrophic myocytes and to fibroblasts.