EXPERIMENTAL CVB3-INDUCED CHRONIC MYOCARDITIS IN 2 MURINE STRAINS - EVIDENCE OF INTERRELATIONSHIPS BETWEEN VIRUS-REPLICATION AND MYOCARDIALDAMAGE IN PERSISTENT CARDIAC INFECTION

In order to analyse the relationships between enteroviral replication and the myocardial damage at the onset of chronic cardiac infection, 2 mouse strains with different degrees of immunological competence (NMR I nu/nu, DBA/2) were infected by a myocarditic Coxsackie virus B3 (CVB 3-M1) variant. At 31 days post-inoculation, plaque-forming assay, poly merase chain reaction (RT-PCR), and immunohistochemistry were carried out for detecting viruses and viral components in the myocardium. The virological findings were related to histopathological changes in the myocardium as well to the dilatation of both cardiac ventricles. Chron ic myocardial lesions characterized by large fibrosis areas and inters titial inflammatory infiltrates were detected together with cardiomega lia in 52.6% (10/19) of athymic mice and in 9% (2/22) of euthymic mice . Viral replication foci were located and were found only in myocardit ic cells adjacent to myocardial inflammatory lesions by immunostaining myocardial tissue sections with anti-serum to VP1 virus capsid protei n. Using PCR followed by microwell capture hybridization assay, a larg e excess of viral positive strand RNA over negative strand was semiqua ntified in heart tissue from mice with chronic myocarditis, whereas ap proximately equal amounts of plus and minus strand RNA were detected i n cases of persistent cardiac infection without chronic myocardial inj uries. These findings provide evidence of the major role of viral repl ication in the pathogenesis of chronic murine CVB3-induced cardiomyopa thy, The results indicate that the cardiac persistence of enteroviral RNAs can be observed without chronic cardiomyopathy, which could be ex plained by a defective viral positive RNA replication. (C) 1997 Wiley- Liss, Inc.