title: Inhibition of coxsackievirus B3 carrier state infection of cultured human myocardial fibroblasts by ribavirin and human natural interferon-alpha.
abstract: As enterovirus infections of the heart cause myocarditis and eventually congestive heart failure, the antiviral activity of ribavirin was studied in coxsackie virus B3 (CVB3)-infected carrier cultures of human myocardial fibroblasts. Cultures were infected 7 days before application of ribavirin and effects were evaluated over a period of 16 days by plaque assays and in situ hybridization. Compared to the low antiviral activity in HeLa cells, ribavirin was highly active in reducing infectious virus yields in human myocardial fibroblasts, for example, to 2.0 x 10(3) pfu/ml with 25 microg/ml and to 1.3 x 10(2) pfu/ml with 50 microg/ml (4.3 x 10(4) pfu/ml in infected controls). Moreover, 100 microg ribavirin/ml completely suppressed infectious virus progeny in two of three cultures, and reduced the number of infected cells from 14.3 to 0.3% as determined by in situ hybridization, whereas up to 3200 microg ribavirin/ml did not result in a significant cytotoxic effect. Interaction with interferon-alpha (IFN-alpha) was additive to slightly synergistic in reducing the number of infected cells and virus yields. In conclusion, our results suggest a cell-specific high activity of ribavirin in human myocardial fibroblasts and indicate the importance of using organ-specific cells for testing antiviral agents in myocarditis. Furthermore, the usefulness of in situ hybridization for determining the long term effects of antivirals in carrier state cell cultures was demonstrated.
authors.affiliation: Institute for Virology, Medizinische Hochschule Hannover, Germany. Albert.Heim@T-Online.de
authors.forename: A
authors.initials: A
authors.lastname: Heim
authors.forename: I
authors.initials: I
authors.lastname: Grumbach
authors.forename: P
authors.initials: P
authors.lastname: Pring-Akerblom
authors.forename: M
authors.initials: M
authors.lastname: Stille-Siegener
authors.forename: G
authors.initials: G
authors.lastname: Müller
authors.forename: R
authors.initials: R
authors.lastname: Kandolf
authors.forename: H R
authors.initials: HR
authors.lastname: Figulla
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002353:Carrier State / Q000188:drug therapy / Q000821:virology; D002460:Cell Line; D003384:Coxsackievirus Infections / Q000188:drug therapy / Q000821:virology; D004357:Drug Synergism; D029822:Enterovirus B, Human / Q000187:drug effects*; D005347:Fibroblasts; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D009205:Myocarditis / Q000188:drug therapy / Q000821:virology; D009206:Myocardium; D012254:Ribavirin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin