INHERITANCE OF INTRACELLULAR VIRAL RNA IN A MULTISCALE MODEL OF HEPATITIS C INFECTION

Area of Science:

• Virology
• Mathematical Biology
• Hepatology

Background:

• Multiscale mathematical models are crucial for understanding hepatitis C virus (HCV) infection and direct-acting antivirals.
• Existing models often focus on intracellular viral production but may oversimplify infected cell proliferation.

Purpose of the Study:

• To develop and analyze a multiscale mathematical model of HCV infection that explicitly incorporates the proliferation of infected hepatocytes.
• To investigate how infected cell division impacts viral persistence and disease dynamics.

Main Methods:

• Development of a multiscale mathematical model for HCV infection.
• Mathematical analysis demonstrating the equivalence to a system of ordinary differential equations (ODEs).
• Bifurcation analysis of the resulting ODE system.

Main Results:

• The model successfully incorporates the inheritance of viral RNA during infected hepatocyte proliferation.
• Bifurcation analysis shows that infected cell proliferation can lead to persistent HCV infection.
• This persistence can occur even when the basic reproductive number (R0) is less than one.

Conclusions:

• Incorporating infected hepatocyte proliferation into multiscale HCV models is essential for accurate dynamics.
• Hepatocyte proliferation is a significant factor that can drive viral persistence, independent of the basic reproductive number.
• The findings offer new insights into HCV persistence mechanisms and potential therapeutic targets.