FIG. 8.

Two models for expansion of virus in the growing liver. The two models differ in the origin of new liver cells during liver growth or turnover. Model 1: infected liver cells divide, resulting in a reduction of cccDNA copy number per nucleus in the progeny cells. New cccDNA molecules (cccDNA∗) are made directly from preexisting rcDNA and linear DNA in the cytoplasm. The additional virus secreted in the serum is derived from the new cccDNA molecules. Model 2: new uninfected hepatocytes are derived from progenitor cells and are infected de novo by rcDNA- and linear DNA-containing virus in the serum. New cccDNA molecules (cccDNA∗) derived from the infecting virus constitute a new pool of cccDNA analogous to the cccDNA molecules synthesized in model 1. rcDNA and linear DNA is synthesized in the newly infected cells and is used for cccDNA amplification (cccDNA∗). Virus secreted in the serum is derived primarily from the amplified cccDNA pool. The spread of infection as described in model 1 results in the secretion of virus that is one generation removed from the previous virus population. In model 2, virus released in the blood is two generations removed from the previous virus population. The first and second generations of virus from cccDNA are indicated as numbered circles.