A Model for Intracellular Trafficking of Adenoviral Vectors

Abstract

Here we develop an integrative computational framework to model biophysical processes involved in viral gene delivery. The model combines reaction-diffusion-advection equations that describe intracellular trafficking with kinetic equations that describe transcription and translation of the exogenous DNA. It relates molecular-level trafficking events to whole-cell distribution of viruses. The approach makes use of the current understanding of cellular processes and data from single-particle single-cell imaging experiments. The model reveals two important parameters that characterize viral transport at the population level, namely, the effective velocity, V eff, and the effective diffusion coefficient, D eff. V eff measures virus’s net movement rate and D eff represents the total dispersion rate. We employ the model to study the influence of microtubule-mediated movements on nuclear targeting and gene expression of adenoviruses of type 2 and type 5 in HeLa and A549 cells. Effects of microtubule organization and the presence of microtubule-destabilizing drugs on viral transport were analyzed and quantified. Model predictions agree well with experimental data available in literature. The paper serves as a guide for future theoretical and experimental efforts to understand viral gene delivery.