Modeling poliovirus replication dynamics from live time-lapse single-cell imaging data

Abstract

Viruses experience selective pressure on the timing and order of events during infection to maximize the number of viable offspring they produce. Additionally, they may experience variability in cellular environments encountered, as individual eukaryotic cells can display variation in gene expression among cells. This leads to a dynamic phenotypic landscape that viruses must face to replicate. To examine replication dynamics displayed by viruses faced with this variable landscape, we have developed a method for fitting a stochastic mechanistic model of viral infection to time-lapse imaging data from high-throughput single-cell poliovirus infection experiments. The model's mechanistic parameters provide estimates of several aspects associated with the virus's intracellular dynamics. We examine distributions of parameter estimates and assess their variability to gain insight into the root causes of variability in viral growth dynamics. We also fit our model to experiments performed under various drug treatments and examine which parameters differ under these conditions. We find that parameters associated with translation and early stage viral replication processes are essential for the model to capture experimentally observed dynamics. In aggregate, our results suggest that differences in viral growth data generated under different treatments can largely be captured by steps that occur early in the replication process.