Proximity between the cap and 5′ ε stem–loop structure is critical for the suppression of pgRNA translation by the hepatitis B viral polymerase

The pregenomic RNA (pgRNA) of hepatitis B virus (HBV) serves as an mRNA as well as an RNA template for viral reverse transcription. We previously reported that HBV Pol (polymerase) suppresses translation of the pgRNA through a mechanism involving the 5´ ε sequence [Virology 373:112–123(2008)]. Here, we found that the recognition of the 5´ ε stem–loop structure by HBV Pol is essential for the translation suppression. Intriguingly, the translation suppression was observed only when the 5´ ε sequence was positioned within approximately 60 nucleotides from the 5′ end, which is striking reminiscent of the pgRNA encapsidation. This finding implicates that the translation suppression is mechanistically linked to encapsidation of the pgRNA. However, unexpectedly, the HBV Pol–eIF4E interaction, which we reported recently [J. Virol. 84:52–58(2010)], is not required for the translation suppression. Instead, the data suggested that the cap proximity of 5´ ε sequence is necessary and sufficient for the translation suppression.