Intracellular Dynamics of Hepatitis B Virus Infection: A Mathematical Model and Global Sensitivity Analysis of Its Parameters

Analysis of cell population can reveal the average information about the viral infection in host whereas single-cell analysis can capture the individual consideration. Single-cell analysis can also provide new ways to explore viral diversities and identify the intrinsic extreme phenotype of the cells. In this study, a single-cell hepatitis B virus (HBV) infection model is proposed by considering all possible intracellular steps which are observed in the viral life cycle. To the best of our knowledge, it is the most generalized model to date. The effects of newly introduced factors or components such as, cccDNA, HBx proteins, surface proteins, and double-stranded linear DNA-containing capsids are explained very well by this model. The intracellular delay is also incorporated into the proposed model, and it is seen that it has no significant impact on the persistence of infection. The global sensitivity analysis of the parameters is also performed using partial rank correlation coefficients based on Latin hypercube sampling method. According to PRCC values, the most positive and most negative sensitive parameters are identified. Moreover, it is observed that the availability of viral surface proteins switches the replication pattern from acute to chronic, whereas there is no considerable contribution of HBx proteins to the progression of HBV infection. Another striking result is that the recycling of capsids appears to act as a positive feedback loop throughout the infection.