Abstract
Translation initiation of hepatitis C virus (HCV) occurs in an internal ribosome entry site (IRES)-dependent manner. We found that HCV IRES-dependent protein synthesis is enhanced by PD98059, an inhibitor of the extracellular signal-regulated kinase (ERK) signaling pathway, while cellular cap-dependent translation was relatively unaffected by the compound. Treatment of cells with PD98059 allowed for robust HCV replication following cellular incubation with HCV-positive serum. Though the molecular mechanism underlying IRES enhancement remains elusive, PD98059 is a potent accelerator of HCV RNA replication.
MeSH terms
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Base Sequence
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Carcinoma, Hepatocellular
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Cell Line, Tumor
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DNA Primers
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Enzyme Inhibitors / pharmacology
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Flavonoids / pharmacology*
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Hepacivirus / drug effects
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Hepacivirus / genetics
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Hepacivirus / physiology*
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Humans
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Liver Neoplasms
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Protein Biosynthesis* / drug effects
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RNA, Small Interfering / genetics
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Ribosomes / drug effects
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Ribosomes / physiology*
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Ribosomes / virology
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Virus Replication / drug effects
Substances
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DNA Primers
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Enzyme Inhibitors
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Flavonoids
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RNA, Small Interfering
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Calcium-Calmodulin-Dependent Protein Kinases
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one