Abstract
Interferon (IFN) therapy is used worldwide as the best available treatment for hepatitis C virus (HCV) infection; however, little is known about how IFN or other drugs work against liver diseases. The effect of 6 drugs (glycyrrhizin, ursodeoxycholic acid, ribavirin, methylprednisolone, IFN-alpha, and IFN-beta) on HCV RNA translation from the HCV internal ribosome entry site (IRES) was investigated, using a bicistronic reporter containing the HCV IRES. IFNs suppressed both cap-dependent and HCV IRES-dependent translation, with HCV IRES-dependent translation being more significantly suppressed. In contrast to HCV IRES, IFN did not suppress either foot-and-mouth disease virus IRES-dependent or encephalomyocarditis virus IRES-dependent translation more than it suppressed cap-dependent translation. Moreover, dominant inhibition of HCV IRES-dependent over cap-dependent translation depended neither on the double-stranded RNA-activated protein kinase activation nor on La protein function. These results indicate a novel antiviral effect of IFNs against HCV.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Infective Agents / pharmacology*
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Antiviral Agents / pharmacology
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Autoantigens / biosynthesis
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Blotting, Western
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Cholagogues and Choleretics / pharmacology
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Encephalomyocarditis virus / metabolism
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Foot-and-Mouth Disease Virus / metabolism
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Glucocorticoids / pharmacology
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Glycyrrhizic Acid / pharmacology
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Hepacivirus / drug effects*
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Hepacivirus / genetics
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Hepacivirus / metabolism
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Humans
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Interferons / metabolism
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Interferons / pharmacology*
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Methylprednisolone / pharmacology
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Protein Biosynthesis / drug effects
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Protein Biosynthesis / physiology
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RNA, Double-Stranded / genetics
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RNA, Double-Stranded / metabolism
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RNA, Viral / genetics
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RNA, Viral / metabolism
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Ribavirin / pharmacology
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Ribonucleoproteins / biosynthesis
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Ribosomes / drug effects*
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Ribosomes / genetics
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Ribosomes / metabolism
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SS-B Antigen
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Tumor Cells, Cultured
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Ursodeoxycholic Acid / pharmacology
Substances
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Anti-Infective Agents
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Antiviral Agents
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Autoantigens
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Cholagogues and Choleretics
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Glucocorticoids
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RNA, Double-Stranded
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RNA, Viral
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Ribonucleoproteins
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Ribavirin
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Glycyrrhizic Acid
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Ursodeoxycholic Acid
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Interferons
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Methylprednisolone