Antiviral activity of CHO-SS cell-derived human omega interferon and other human interferons against HCV RNA replicons and related viruses

The fully glycosylated human omega interferon produced from CHO-SS cells (glycosylated IFN-ω) has been shown to be well-tolerated in man and to induce a sustained virologic response in patients infected with hepatitis C virus (HCV). We examined the antiviral activity of glycosylated IFN-ω and various human IFNs (IFN-α, -β, -γ and non-glycosylated bacterial (Escherichia coli) recombinant IFN-ω (non-glycosylated IFN-ω)) against HCV RNA replicons and several viruses related to HCV. Since none of the IFNs displayed cytotoxicity we compared their activities based on the effective concentration of the IFN that inhibited virus growth by 50% (EC50). Glycosylated IFN-ω was found to be the most potent antiviral agent of all the IFNs tested against bovine viral diarrhea virus (BVDV), yellow fever virus and West Nile virus. With HCV RNA replicons, non-glycosylated IFN-ω was comparable in activity to IFN-α while glycosylated IFN-ω was markedly more potent, indicating that glycosylation has an important effect on its activity. Drug combination analysis of glycosylated IFN-ω + ribavirin (RBV) in BVDV showed a synergy of antiviral effects similar to IFN-α + RBV, as well as a unique antagonism of RBV cytotoxic effects by glycosylated IFN-ω. Transcription factor (TF) profiling indicated that IFN-α or glycosylated IFN-ω treatment upregulated the same 17 TFs. IFN-α and glycosylated IFN-ω also upregulated 9 and 40 additional unique TFs, respectively. The differences in the expression of these TFs were modest, but statistically significantly different for eight of the TFs that were upregulated exclusively by glycosylated IFN-ω. The activation of these additional TFs by glycosylated IFN-ω might contribute to its high potency.