ABSTRACT
The DNA genome of a hepatitis B virus is generated by reverse transcription of the RNA pregenome. Replication initiation does not involve a nucleic acid primer; instead, the hepadnavirus P protein binds to the structured RNA encapsidation signal ɛ, from which it copies a short DNA primer that becomes covalently linked to the enzyme. Using in vitro-translated duck hepatitis B virus (DHBV) P protein, we probed the secondary structure of the protein-bound DHBV ɛ RNA (Dɛ) and observed a marked conformational change compared to free Dɛ RNA. Several initiation-competent mutant RNAs with a different free-state structure were similarly altered, whereas a binding-competent but initiation-deficient variant was not, indicating the importance of the rearrangement for replication initiation and suggesting a mechanistic coupling to encapsidation.
A Small 2′-OH- and Base-dependent Recognition Element Downstream of the Initiation Site in the RNA Encapsidation Signal Is Essential for Hepatitis B Virus Replication Initiation
