The 5 ' untranslated region of GB virus B shows functional similarity to the internal ribosome entry site of hepatitis C virus

Since its characterization in 1995, there has been increasing interest in t he significance of GB virus B (GBV-B) due to its close phylogenetic relatio nship to hepatitis C virus (HCV). The genome of GBV-B is similar in length and organization to that of HCV and the two viruses share sequence similari ty in their 5' untranslated regions (5'UTR). A secondary structure model of the GBV-B 5'UTR has been proposed by comparative sequence analysis with HC V. The highly conserved secondary structure, present in HCV and the pestivi ruses, is also present in the 5'UTR of GBV-B. Translation of the HCV polypr otein initiates via an internal ribosome entry site (IRES) and it is propos ed that the GBV-B UTR may function in a similar manner. Dicistronic reporte r constructs were made to investigate the function of the GBV-B 5'UTR. Muta tional analysis and in vitro translation experiments demonstrate that GBV-B initiates translation via an IRES.