The pathway of HCV IRES-mediated translation initiation

Cell. 2004 Oct 29;119(3):369-80. doi: 10.1016/j.cell.2004.09.038.


The HCV internal ribosome entry site (IRES) directly regulates the assembly of translation initiation complexes on viral mRNA by a sequential pathway that is distinct from canonical eukaryotic initiation. The HCV IRES can form a binary complex with an eIF-free 40S ribosomal subunit. Next, a 48S-like complex assembles at the AUG initiation codon upon association of eIF3 and ternary complex. 80S complex formation is rate limiting and follows the GTP-dependent association of the 60S subunit. Efficient assembly of the 48S-like and 80S complexes on the IRES mRNA is dependent upon maintenance of the highly conserved HCV IRES structure. This revised model of HCV IRES translation initiation provides a context to understand the function of different HCV IRES domains during translation initiation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • HeLa Cells
  • Hepacivirus / genetics*
  • Hepacivirus / metabolism
  • Hepatitis C / genetics*
  • Hepatitis C / metabolism
  • Humans
  • Molecular Sequence Data
  • Protein Biosynthesis / physiology
  • RNA, Viral / metabolism*
  • Ribosomal Proteins / metabolism
  • Ribosomes / metabolism*
  • Sucrose / metabolism


  • RNA, Viral
  • Ribosomal Proteins
  • Sucrose