Identification of a cellular protein required for hepatitis C virus internal ribosome entry site (IRES)-mediated translation

摘要

Hepatitis C virus (HCV) infection frequently leads to chronic hepatitis and cirrhosis of the liver, and has been linked to the development of hepatocellular carcinoma. Currently, the standard therapy for HCV infection consists of inter fer on (IFN) alone or in combination with ribavirin, with a rather low and variable sustained response rate; therefore, alternative drugs targeting viral or cellular factors are urgently neededThe HCV genome is a positive, single-strand RNA molecule encoding one polyprotein of about 3000 amino acids. HCV-RNA exists as a quasispecies-a mixture of highly related but distinct viral RNA sequences. The translation of HCV genomic RNA is cap-independent and mediated by an internal ribosome entry site (IRES) located at the 5'UTR1 In contrast to the other part of HCV genome the 5'UTR is highly conserved. In addition to the standard initiation factors, the initiation events directed by IRES require other trans-acting cellular factors. These cellular factors are potential drug targets for the inhibition of HCV replication.