Model for HCTD and DCTD effects on DHBc phosphorylation, core DNA synthesis, and CCC DNA formation through interactions with different host factors. Shown schematically is a simplified diagram of the DHBV life cycle, with its major steps highlighted. The interactions between the HCTD and DCTD variants with the host CDK2, importin α, a putative cellular phosphatase (PPase), or unknown factors (indicated by the question marks) are proposed to sequester these factors so that they are unavailable for interactions with the CTD on the full-length core protein, thus inhibiting viral replication at the various steps. The gray letters in parentheses denote that those fusion proteins fail to interact with the relevant host factors. The capsid is depicted as hexagons, and capsid phosphorylation is denoted by the letter “P” inside the circles. The dashed line of the mature NCs (i.e., containing RC DNA) denotes the fact that they are less stable than the immature NCs (i.e., containing pgRNA or SS DNA). RC, relaxed circular DNA; SS, single-stranded DNA; CCC, covalently closed circular DNA. See the text for details.