PREDICTED SECONDARY STRUCTURE OF THE HEPATITIS-G VIRUS AND GB VIRUS-A5'-UNTRANSLATED REGIONS CONSISTENT WITH AN INTERNAL RIBOSOME ENTRY SITE

We describe comparative sequence analysis of 20 isolates of the recent ly discovered hepatitis G virus (HGV) and propose a model of the RNA s econdary structure at the 3' end of the 5' untranslated region (UTR) o f this virus. A single AUG starting at nucleotide position 552, which was in-frame and continuous with the putative polyprotein, was conserv ed in all 20 isolates and appeared to be the most likely site for the initiation of polyprotein synthesis, This consensus AUG was 14 amino a cid residues upstream of a sequence with identity to the envelope prot ein E1 of hepatitis C virus (HCV), but the actual function of this N-t erminal peptide of HGV is still not certain. None of the isolates enco ded a sequence with similarity to the nucleocapsid protein of any know n virus, The RNA secondary structure of the fragment under study was d etermined using thermodynamic modelling and validated using the result s of comparative sequence analysis. Further support for the model was gained from the prediction of significant sequence and structural homo logy in the RNA secondary structure of the complete 5'-UTR of GB virus -A (GBV-A). A possible mechanism for translation initiation in HGV and GBV-A was suggested by the identification of features in common with the internal ribosome entry sites (IRESs) of HCV and picornaviruses.