(A) Theoretical Study of Recycling Effects of rcDNA-containing Capsids on Hepatitis B Virus Infection

Abstract

In this thesis, the dynamics of hepatitis B virus (HBV) infection are studied by incorporating several aspects, such as recycling of capsids, the effects of fractional-order derivative, the impacts of proliferation, the roles of sub-viral particles and antibodies. This dissertation begins by investigating the roles of cytoplasmic recycling of rcDNA-containing capsids in HBV infection. To this purpose, a novel four-compartmental (uninfected and infected hepatocyte, rcDNA-containing capsids and virus) ODE model is proposed to better understand this viral infection. This model demonstrates excellent agreement with the experimental data of two chimpanzees. The effects of three key parameters (recycling rate, virus production rate, and volume fraction of newly produced capsids in favor of virus production) are analyzed via numerical experiments. Furthermore, a comprehensive global sensitivity analysis is conducted using the widely-used technique Latin hypercube sampling–partial rank correlation coefficient. As a result, this study shows that the accumulation of rcDNA-containing capsids within the infected hepatocyte is a key factor contributing to the exacerbation of the disease. In other words, the cytoplasmic recycling of newly produced rcDNA-containing capsids acts as a positive feedback loop in the viral infection.