Working model for HBc linker functions at multiple stages of HBV replication.

<p>The linker is proposed to exert its effects on capsid assembly via the NTD, its effects on pgRNA packaging and DNA synthesis via the CTD, and its effects on virion secretion via interaction with the envelope proteins. Capsids are denoted by the hexagons, the viral envelope by the circles, pgRNA by the wavy line, SS DNA by the straight line, and RC DNA by the broken double concentric circle with the arrow pointing to the 3’ end of the plus strand. The broken line of the RC DNA-containing (i.e., mature) NCs denotes the fact that mature NCs are destabilized. The red lines denote inhibitory or negative effects; green lines, stimulatory or positive. The putative mediators of the negative and positive effects are also indicated, including conformation–NTD or CTD conformations involved in assembly or the other indicated aspects of HBc functions; putative host factors (HF) regulating capsid assembly; host protein kinase or protein phosphatase (PPase) that control CTD state of phosphorylation. The putative interactions between the HBc linker and the envelope proteins in virion secretion are also denoted with the green lines. seq, sequence; (in)depend, (in)dependent; *, secretion of empty virions being the most sequence-specific function of the linker. See text for details.