Schematic diagram of multiscale modeling of intracellular and intercellular infection.

The entry virion forms cccDNA in the nucleus and produces intracellular HBV DNA at rate α. HBsAg, HBeAg, and HBcrAg antigens are also produced from cccDNA at rates π_S, π_E, and π_R and cleared at σ in peripheral blood, respectively. Additionally, HBsAg may also be produced by integrated HBV DNA (iDNA) in the infected cells at a rate s_i. The intracellular HBV DNA is consumed at rate ρ, of which a fraction 1−f of HBV DNA assembled with viral proteins as virus particles are exported from infected cells and the other fraction f is reused for further cccDNA formation having a degradation rate of d. The infected cells are dead at rate δ and the exported viral particles, which are cleared at rate μ, infect their target cells at rate β.