Inheritance of Intracellular Viral RNA in a Multiscale Model of Hepatitis C Infection

Multiscale mathematical models of hepatitis C infection have been instrumental in our understanding of direct acting antivirals. These models include the mechanisms driving intracellular viral production and explicitly model the intracellular concentration of viral RNA. However, incorporating proliferation of infected hepatocytes in these models can be subtle, as infected daughter cells inherit viral RNA from the proliferating mother cell. Here, we show how to incorporate this inheritance within a multiscale model of HCV infection. As in typical multiscale models of HCV infection, we show that this model is mathematically equivalent to a system of ordinary differential equations and perform bifurcation analysis of the resulting ODE that demonstrates that proliferation of infected hepatocytes can lead to infection persistence even if the basic reproductive number is less than one.