title: Antiviral activity of CHO-SS cell-derived human omega interferon and other human interferons against HCV RNA replicons and related viruses.
abstract: The fully glycosylated human omega interferon produced from CHO-SS cells (glycosylated IFN-omega) 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-omega and various human IFNs (IFN-alpha, -beta, -gamma and non-glycosylated bacterial (Escherichia coli) recombinant IFN-omega (non-glycosylated IFN-omega)) 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-omega 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-omega was comparable in activity to IFN-alpha while glycosylated IFN-omega was markedly more potent, indicating that glycosylation has an important effect on its activity. Drug combination analysis of glycosylated IFN-omega+ribavirin (RBV) in BVDV showed a synergy of antiviral effects similar to IFN-alpha+RBV, as well as a unique antagonism of RBV cytotoxic effects by glycosylated IFN-omega. Transcription factor (TF) profiling indicated that IFN-alpha or glycosylated IFN-omega treatment upregulated the same 17 TFs. IFN-alpha and glycosylated IFN-omega 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-omega. The activation of these additional TFs by glycosylated IFN-omega might contribute to its high potency.
authors.affiliation: Veracity Biotechnology, LLC, 401 Rosemont Avenue, Third Floor Rosenstock Hall, Frederick, MD 21701, USA. vbuckwold@veracitybiotech.com
authors.forename: Victor E
authors.initials: VE
authors.lastname: Buckwold
authors.forename: Jiayi
authors.initials: J
authors.lastname: Wei
authors.forename: Zhuhui
authors.initials: Z
authors.lastname: Huang
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Huang
authors.forename: Aysegul
authors.initials: A
authors.lastname: Nalca
authors.forename: Jay
authors.initials: J
authors.lastname: Wells
authors.forename: Julie
authors.initials: J
authors.lastname: Russell
authors.forename: Barbara
authors.initials: B
authors.lastname: Collins
authors.forename: Roger
authors.initials: R
authors.lastname: Ptak
authors.forename: William
authors.initials: W
authors.lastname: Lang
authors.forename: Curtis
authors.initials: C
authors.lastname: Scribner
authors.forename: Dennis
authors.initials: D
authors.lastname: Blanchett
authors.forename: Tom
authors.initials: T
authors.lastname: Alessi
authors.forename: Peter
authors.initials: P
authors.lastname: Langecker
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000276:immunology / Q000494:pharmacology*; D016466:CHO Cells; D002417:Cattle; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D004338:Drug Combinations; D016174:Hepacivirus / Q000235:genetics*; D006801:Humans; D007370:Interferon Type I / Q000276:immunology / Q000494:pharmacology*; D007372:Interferons / Q000276:immunology / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D012093:Replicon / Q000187:drug effects* / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D004338:Drug Combinations; D007370:Interferon Type I; D011994:Recombinant Proteins; D014157:Transcription Factors; C063743:interferon omega 1; D007372:Interferons