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Anti‐hepatitis C virus activity of albinterferon alfa‐2b in cell culture
Author(s) -
Liu Chen,
Zhu Haizhen,
Subramanian G. Mani,
Moore Paul A.,
Xu Yiling,
Nelson David R.
Publication year - 2007
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2007.00142.x
Subject(s) - hepatitis c virus , interferon , pegylated interferon , virology , albumin , hepatitis c , liver cell , immunology , recombinant dna , medicine , virus , cell , interferon alfa , alpha interferon , ribavirin , biology , gene , biochemistry
Background: Interferon‐based combination therapy is the standard treatment for chronic hepatitis C virus (HCV) infection. The weekly administration of long‐acting pegylated interferons (PEG‐IFNα‐2a or PEG‐IFNα‐2b) provides superior antiviral efficacy over standard interferon alfa (IFNα) for the treatment of HCV infection. Albinterferon alfa‐2b (alb‐IFN) is a novel recombinant protein consisting of IFNα‐2b that is genetically fused to human albumin. Methods: To test alb‐IFN antiviral efficacy, we compared the antiviral activity of unmodified IFNα with the three modified interferons (PEG‐IFNα‐2a, PEG‐IFNα‐2b, and alb‐IFN) at clinically relevant serum concentrations using liver cell‐based and non‐liver cell‐based HCV replicon cell lines. The EC 50 in GSB cells for IFNα‐2b, PEG‐IFNα‐2a, PEG‐IFNα‐2b and alb‐IFN was 7 U/mL, 1.1 ng/mL, 18 ng/mL, and 15 ng/mL, respectively. Results: At clinically relevant patient serum concentrations, alb‐IFN exhibits more antiviral activity than the pegylated interferons. Alb‐IFN showed similar inhibition of HCV replication in human liver cells and non‐liver cells, indicating it has anti‐HCV activity in non‐liver cells. The magnitude of induction of interferon‐stimulated genes ( MxA , 2′5′ OAS1 , IFI44 , and IFI27 ) at 6 h and 48 h was comparable for all the modified IFNs in human liver cells at the drug concentrations evaluated. Conclusion: The present study indicates that alb‐IFN has a potent, direct anti‐HCV activity in both liver and non‐liver cells.