Enhancement of internal ribosome entry site-mediated translation and replication of hepatitis C virus by PD98059.
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.
Murata
Takayuki
T
Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Hijikata
Makoto
M
Shimotohno
Kunitada
K
D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D017931:DNA Primers; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms; D014176:Protein Biosynthesis / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D012270:Ribosomes / Q000187:drug effects / Q000502:physiology* / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
D017931:DNA Primers; D004791:Enzyme Inhibitors; D005419:Flavonoids; D034741:RNA, Small Interfering; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one