TY - JOUR
T1 - Anti-hepatitis C virus activity of albinterferon alfa-2b in cell culture
AU - Liu, Chen
AU - Zhu, Haizhen
AU - Subramanian, Mani G.
AU - Moore, Paul A.
AU - Xu, Yiling
AU - Nelson, David R.
PY - 2007/11
Y1 - 2007/11
N2 - 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.
AB - 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.
KW - Albinterferon alfa-2b
KW - Gene expression
KW - Hepatitis C virus
KW - Replicon
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U2 - 10.1111/j.1872-034X.2007.00142.x
DO - 10.1111/j.1872-034X.2007.00142.x
M3 - Article
C2 - 17573950
AN - SCOPUS:34548610612
SN - 1386-6346
VL - 37
SP - 941
EP - 947
JO - Hepatology Research
JF - Hepatology Research
IS - 11
ER -