Re-cycling of DNA-containing Capsids Enhances Hepatitis B Virus Infection

TL;DR

This study models how recycling of DNA-containing capsids in hepatitis B virus enhances infection dynamics, revealing that capsid recycling acts as a positive feedback loop increasing virus proliferation and disease severity.

Contribution

It introduces a novel four-compartment mathematical model incorporating capsid recycling effects, providing new insights into HBV infection dynamics and stability.

Findings

Capsid recycling significantly increases virus release.

Recycling creates a positive feedback loop in infection.

Capsid accumulation worsens disease progression.

Abstract

Hepatitis B virus infection is a deadly liver disease. A part of newly produced HBV DNA-containing capsids are reused as a core particle in HBV replication. It is investigated that the recycling of HBV capsids greatly affects the intracellular dynamics of HBV infection. The main purpose of the present work is to study the recycling effects of HBV DNA-containing capsids in the HBV infection. Incorporating recycling effects of capsids, a four-compartment mathematical model is proposed for the first time in order to understand the dynamics of HBV infection in a better way. The well-posedness of the model is obtained by showing non-negativity, boundedness, and uniqueness of the solution. The explicit formula for the basic reproduction number is determined by applying the next-generation approach method. The proposed model is solved with help of fourth-order explicit Runge-Kutta method. Through a rigorous comparison with experimental data obtained from four chimpanzees, the proposed model demonstrates a strong correspondence with the dynamics of HBV infection. Global sensitivity analysis is also conducted to identify the most positively as well as negatively sensitive parameters for each compartment in the model. In the context of biology, depending on the value of basic reproduction number, the present model possesses two global asymptotically stable steady states: disease-free and endemic. The present study shows that the consideration of recycling of capsids reverses the existing mechanism of infection dynamics. This study also reveals that the accumulation of capsids within the infected hepatocytes is a key factor for exacerbating the disease. Moreover, another major finding of our study is that due to recycling of capsids, the number of released virus increases in spite of low virus production rate. The recycling of capsids acts as a positive feedback loop in the viral infection.