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"Liver-on-a-Chip" Cultures of Primary Hepatocytes and Kupffer Cells for Hepatitis B Virus Infection
Published on: February 19, 2019
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Exploration of Hepatitis B Virus Infection Dynamics through an Intracellular Model
Rupchand Sutradhar1, Durga Charan Dalal1
1Department of Mathematics, Indian Institute of Technology Guwahati, Guwahati, Assam, India.
Journal of Theoretical Biology
|June 16, 2025
Summary
This study developed an intracellular hepatitis B virus (HBV) model to analyze infection dynamics. HBx proteins significantly impact HBV infection, while capsid recycling amplifies viral replication within cells.
Area of Science:
- Virology
- Mathematical Biology
- Infectious Diseases
Background:
- Traditional population-level analysis of viral infections offers limited insight into individual cell responses.
- Understanding intracellular dynamics is crucial for comprehending the complete viral life cycle and infection progression.
- Hepatitis B virus (HBV) infection involves complex intracellular mechanisms that warrant detailed investigation.
Purpose of the Study:
- To develop and analyze an intracellular mathematical model for hepatitis B virus (HBV) infection dynamics.
- To identify key factors influencing HBV infection at the individual cellular level.
- To assess the impact of specific viral components and host-cell interactions on infection progression.
Main Methods:
- Development of an intracellular HBV infection dynamics model incorporating key viral life cycle steps.
- Numerical solution of the model using the fourth-order Runge-Kutta method.
- Global sensitivity analysis, employing Latin hypercube sampling-partial rank correlation coefficients, to identify influential parameters.
Main Results:
- Model simulations showed good agreement with experimental data.
- Hepatitis B virus X (HBx) proteins were identified as having a significant impact on infection dynamics.
- Intracellular delay and dslDNA intermediates demonstrated minimal influence on infection progression, while capsid recycling significantly enhanced cccDNA amplification.
Conclusions:
- HBx proteins play a critical role in modulating intracellular HBV infection.
- Capsid recycling is a key mechanism for amplifying covalently closed circular DNA (cccDNA) and enhancing HBV infection.
- Sub-viral particles may also contribute to the overall progression of hepatitis B virus infection.
Keywords:
Global sensitivity analysisHepatitis BIntracellular modelPartial rank correlation coefficientcccDNAMore Related Videos
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