[Study of the antiviral mechanism of action of ribavirin in the bovine viral diarrhea virus model].
OBJECTIVE
Due to the absence of a cell culture model for HCV, this study evaluated the hypothesis of lethal mutagenic activity of the guanosin analogue ribavirin in HCV, using the BVDV model.


METHODS
First the capacity of ribavirin to inhibit BVDV replication in cell culture was studied. We then amplified by RT-PCR the 5'NTR and NS5B regions of BVDV in the supernatants of BVDV-infected cell cultures treated with increasing concentrations of ribavirin. The PCR products were then sequenced to detect potential mutations.


RESULTS
At a phenotypic level, the inhibition of BVDV replication by ribavirin was most potent when ribavirin was administered soon after BVDV inoculation. These results show a direct antiviral effect of ribavirin on BVDV at an early stage of the viral cycle. At a genotypic level, ribavirin decreased viral RNA levels.


CONCLUSIONS
This study shows that ribavirin directly inhibits BVDV replication. These results could explain the synergistic effect of ribavirin and IFN in combined therapy in chronic carriers of HCV. This effect must be confirmed with subgenomic replicons of HCV.
INSERM U271, Virus des Hépatites et Pathologies Associées, 151, cours Albert Thomas, 69424 Lyon Cedex 03, France.
Vanessa
V
Escuret
Parviz
P
Parvaz
Olivier
O
Hantz
Marie-Anne
MA
Petit
Christian
C
Trepo
Fabien
F
Zoulim
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D002417:Cattle; D002460:Cell Line; D001908:Diarrhea Viruses, Bovine Viral / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects; D008954:Models, Biological; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012254:Ribavirin / Q000008:administration & dosage / Q000494:pharmacology*; D016415:Sequence Alignment; D017421:Sequence Analysis; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D012367:RNA, Viral; D012254:Ribavirin