FIG 12.

Model for CDK2/cyclin regulation of HBV NC assembly and disassembly during intracellular CCC DNA amplification and de novo infection. HBc subunits are heavily phosphorylated at the CTD in the cytoplasm by host protein kinases, including the CDK2/cyclin complex and others, and are partially dephosphorylated during pgRNA packaging by PP1. CDK2/cyclin is packaged into immature NCs during NC assembly. HBc is subsequently further dephosphorylated by PP2A during NC maturation. Rephosphorylation of the mature NC in the virion during infection triggers NC disassembly (uncoating) to facilitate release of the RC DNA to the nucleus for CCC DNA formation. During intracellular CCC DNA amplification, cellular kinases from the cytoplasm may phosphorylate HBc in the mature NC to initiate its disassembly such that the packaged kinase may not be essential for uncoating in this pathway of CCC DNA formation. See the text for details.