Translational enhancement of HCV RNA genotype 1b by 3′-untranslated and envelope 2 protein-coding sequences

HCV RNA has a unique regulatory mechanism for translation. The X region of 3′-UTR and core-coding sequence regulate HCV translation. In this study, we clarified that the entire 3′-UTR also enhances HCV translation, and the envelope-coding sequence of HCV genotype 1b increases degree of this enhancement. In the luciferase reporter assay using rabbit reticulocyte lysates, translational enhancement by 3′-UTR with core to E2 regions was 25-fold higher when compared with control RNA lacking the 3′-UTR. Presence of the entire E2 sequence was important for this enhancement. This phenomenon was not due to transcript stability, and envelope protein alone did not affect translation. E2-coding sequence of genotype 1a had no effect on translation. We observed the same results in animal cell culture systems using bicistronic RNA. Structural protein-coding sequences and 3′-UTR of HCV RNA regulate viral translation, and a target for antiviral agents may be present in these regions.