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 (IPES)-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. (c) 2005 Elsevier Inc. All rights reserved.