Key roles of the P protein - ε RNA interaction in HBV replication.

<p>The line with the hairpin structures represents the terminally redundant pgRNA which also serves as mRNA for core protein and P protein; ε and the direct repeats DR1, DR2 and DR1* are indicated. Binding of P to ε initiates their co-encapsidation, and also protein-primed reverse transcription. In this priming reaction, the 3′ nucleotide of the ε bulge and/or the first nucleotide of the upper stem (termed A1 in this study) template the covalent addition of the first DNA nucleotide to a Tyr residue in the TP domain (not explicitly shown) and its extension by two or three nucleotides along the bulge. Upon translocation to a matching acceptor site in DR1* the oligonucleotide is extended into full-length minus-strand DNA, with concomitant degradation of the pgRNA. Subsequent plus-strand synthesis (not shown) eventually yields the relaxed circular (RC) DNA found in virions. The differing shapes of ε and P symbolize conformational alterations that are as yet only well established for DHBV.</p>