Molecular probes for detection of persisting enterovirus infection of human heart and their prognostic value

Abstract

Enteroviruses are well recognized in the aetiology of myocarditis. Molecular hybridization using enterovirus group-specific probes shows that virus can be detected in endomyocardial biopsies and persists in myocardium after the inflammation heals. Virus persistence is associated with the subsequent development of dilated cardiomyopathy, progressing to end-stage disease requiring cardiac transplantation. Infectious virus cannot usually be isolated from myocardium nor can virus-specific antigens be detected after the initial inflammatory stage. Patients with healed myocarditis or dilated cardiomyopathy may have no histological evidence of inflammation despite detection of virus-specific RNA sequences by molecular hybridization. Persisting enterovirus RNA in dilated cardiomyopathy is the strongest known predictor of poor prognosis. The molecular mechanism of virus persistence is the selection of defective virus mutants during the initial phase of disease.