Fig 6.

Proposed mechanisms of suppression of HBV replication by the V124W mutant. In WT capsid assembly, core proteins assemble around the pgRNA-reverse transcriptase complex to form an RNA-filled capsid, in which pgRNA can be reverse transcribed to rcDNA. For V124W capsid assembly, we propose three possible explanations for the observed suppression in DNA synthesis. (i) The V124W mutant might nucleate assembly in the absence of the pgRNA-reverse transcriptase complex to form empty particles or package nonviral RNAs. (ii) The V124W mutant may assemble into kinetically trapped intermediates which do not support reverse transcription, or it may produce viral DNA which can be digested during intracellular capsid DNA isolation. (iii) The V124W mutant may assemble into pgRNA-filled capsids; however, the physical chemistry of the V124W capsid, with its unusually strong association energy, may adversely affect reverse transcription.