Enhanced antiviral effect in cell culture of type 1 interferon and ribozymes targeting HCV RNA

We have recently shown that the replication of an HCV-poliovirus (PV) chime ra that is dependent upon the hepatitis C virus (HCV) 5' untranslated regio n (UTR) can be inhibited by treatment with ribozymes targeting HCV RNA. To determine the antiviral effects of anti-HCV ribozyme treatment in combinati on with type 1 interferon (IFN), we analysed the replication of this HCV-PV chimera in HeLa cells treated with anti-HCV ribozyme and/or IFN-alpha 2a, 1FN-alpha 2b, or consensus IFN. The anti-HCV ribozyme, or any of the IFNs a lone have significant inhibitory effects on HCV-PV replication compared to control treatment (greater than or equal to 85%, P<0.01). The maximal inhib ition due to IFN treatment (94%, P<0.01) was achieved with greater than or equal to 50 U/ml for either IFN-alpha 2a or IFN-alpha 2b compared to contro l treatment. A similar level of inhibition in viral replication could be ac hieved with a 5-fold lower dose of IFN if ribozyme targeting the HCV 5' UTR was given in combination. For consensus IFN, the dose could be reduced by >12.5-fold if ribozyme targeting the HCV 5' UTR was given in combination. C onversely, the dose of ribozyme could be reduced 3-fold if given in combina tion with any of the IFN preparations. Moreover, treatment with low doses ( 1-25 U/mL) of IFN-alpha 2a, IFN-alpha 2b, or consensus IFN in combination w ith anti-HCV ribozyme resulted in >98% inhibition of HCV-PV replication com pared to control treatment (P<0.01). These results demonstrate that IFN and ribozyme each have a beneficial antiviral effect that is augmented when gi ven in combination.