INHIBITION OF COXSACKIEVIRUS B3 CARRIER STATE INFECTION OF CULTURED HUMAN MYOCARDIAL FIBROBLASTS BY RIBAVIRIN AND HUMAN NATURAL INTERFERON-ALPHA

As enterovirus infections of the heart cause myocarditis and eventuall y congestive heart failure, the antiviral activity of ribavirin was st udied in coxsackie virus B3 (CVB3)-infected carrier cultures of human myocardial fibroblasts. Cultures were infected 7 days before applicati on of ribavirin and effects were evaluated over a period of 16 days by plaque assays and in situ hybridization. Compared to the low antivira l activity in HeLa cells, ribavirin was highly active in reducing infe ctious virus yields in human myocardial fibroblasts, for example, to 2 .0 x 10(3) pfu/ml with 25 mu g/ml and to 1.3 x 10(2) pfu/ml with 50 mu g/ml (4.3 x 10(4) pfu/ml in infected controls). Moreover, 100 mu g ri bavirin/ml completely suppressed infectious virus progeny in two of th ree cultures, and reduced the number of infected cells from 14.3 to 0. 3% as determined by in situ hybridization, whereas up to 3200 mu g rib avirin/ml did not result in a significant cytotoxic effect. Interactio n with interferon-alpha (IFN-alpha) was additive to slightly synergist ic in reducing the number of infected cells and virus yields. In concl usion, our results suggest a cell-specific high activity of ribavirin in human myocardial fibroblasts and indicate the importance of using o rgan-specific cells for testing antiviral agents in myocarditis. Furth ermore, the usefulness of in situ hybridization for determining the lo ng term effects of antivirals in carrier state cell cultures was demon strated. (C) 1997 Elsevier Science B.V.