Incorporating time-varying viral production in virus dynamics models

Mathematical modeling of viral kinetics can be used to gain further insight into the viral replication cycle and virus-host interactions. However, many virus dynamics models assume that viral production occurs at a constant rate over the lifespan of the infected cell. In fact, virus yield is time-dependent, which could alter the time course of the viral infection. We used measurements of viral yield from single cells infected with vesicular stomatitis virus (VSV) to determine the cumulative distribution of virus produced by a single cell. We then incorporate the distribution into an integro-differential equation model of viral infection that allows for time-dependent viral production, allowing us to determine how time-dependent viral production changes the predictions of viral kinetics models. We find that time-dependent viral production leads to more rapid decay of the viral load and to changes in the time of viral peak, both of which are important features from a patient standpoint. Including a more realistic implementation of viral production could help improve the accuracy of model predictions.