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Analysis of cell population can reveal the average information about theviral infection in host whereas single-cell analysis can capture the individualconsideration. Single-cell analysis can also provide new ways to explore viraldiversities and identify the intrinsic extreme phenotype of the cells. In thisstudy, a single-cell hepatitis B virus (HBV) infection model is proposed byconsidering all possible intracellular steps which are observed in the virallife cycle. To the best of our knowledge, it is the most generalized model todate. The effects of newly introduced factors or components such as, cccDNA,HBx proteins, surface proteins, and double-stranded linear DNA-containingcapsids are explained very well by this model. The intracellular delay is alsoincorporated into the proposed model, and it is seen that it has no significantimpact on the persistence of infection. The global sensitivity analysis of theparameters is also performed using partial rank correlation coefficients basedon Latin hypercube sampling method. According to PRCC values, the most positiveand most negative sensitive parameters are identified. Moreover, it is observedthat the availability of viral surface proteins switches the replicationpattern from acute to chronic, whereas there is no considerable contribution ofHBx proteins to the progression of HBV infection. Another striking result isthat the recycling of capsids appears to act as a positive feedback loopthroughout the infection.

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