Modelling early viral dynamics of FMDV in vivo

To quantify and predict virus excretion and infectiousness of animals infected with foot-and-mouth disease virus (FMDV), an understanding of the virus dynamics in individual animals is needed. In this paper FMDV dynamics in vivo are described in mathematical terms and possible biological mechanisms suggested to explain the discrepancies between the mathematical model and the experimental data. The model described virus concentrations in the circulation and interstitial space, as well as uninfected and infected epithelial cells. The model was fitted to dose-response curves obtained from pigs inoculated with tenfold different doses of FMDV O UKG 34/2001 by intravenous injection (12 pigs in total, 4 pigs per treatment group, 3 treatments). The model qualitatively reproduced the decrease of FMDV in the circulation seen after intravenous inoculation, followed by an increase of FMDV due to replication of the virus in epithelial cells. The model output showed much smaller differences in the timing of viraemia curves between treatment groups than was indicated by the experimental data. The data were better described by a modified model, in which the rate of infection of epithelial cells at low FMDV concentrations was limited. The modified model was able to accurately describe early FMDV dynamics in vivo. Further theoretical and experimental work suggested by the modelling exercise is discussed