Illustration of the three growth-stage model ofr HBV replication in 1.3ES2 cells. The growth curve of HBV can be separated into three phases: (I) the initial proliferation phase; (II) the exponential proliferation phase; and (III) the growth confluency phase. In the initial proliferation phase, the increase in cccDNA replenishment in the nucleus during the initial cellular proliferation generates a dramatic increase in HBV cccDNA inside the cells. The increased secretion of HBV capsids and low levels of cellular transcription factors explain the relative inactive HBV replication and the inefficient viral transcription inside the cells. In the exponential proliferation phase, the cccDNA decreases significantly, probably because of the dilution effect caused by cell division. The viral transcripts and intracellular nucleocapsids gradually increase in this stage. In the growth confluency phase, HBV transcription dramatically elevates with the increase in cellular transcription factors as the cells reach confluence. Meanwhile, the gradual accumulation of cccDNA and intracellular viral particles, together with elevated viral secretion are observed in these confluent cells.