Hepatitis B virus polymerase suppresses translation of pregenomic RNA via a mechanism involving its interaction with 5′ stem–loop structure

The pregenomic RNA (pgRNA) of hepadnaviruses serves a dual role: as mRNA for the core (C) and polymerase (P) synthesis and as an RNA template for viral genome replication. A question arises as to how these two roles are regulated. We hypothesized that the P protein could suppress translation of the pgRNA via its interaction with 5′ stem–loop structure (ε or encapsidation signal). Consistent with the hypothesis, we observed up-regulation of the C protein level in the absence of the P protein expression in a physiological context. Importantly, translational suppression depended on the 5′ ε sequence. Furthermore, the impact of the P protein on ongoing translation of the C ORF was directly demonstrated by polysome distribution analysis. We conclude that the P protein suppresses translation of the pgRNA via a mechanism involving its interaction with the 5′ ε sequence, a finding that implicates the coordinated switch from translation to genome replication.