Persistence of Foot-and-Mouth disease virus in epithelial cells

A problem presented at the UK MMSG Southampton 2007.

Presented by:
Dr David Schley (Institute for Animal Health)
Dr Zhidong Zhang (Institute for Animal Health)
E Aydemir, K Heymer, D Schley, A Setchi, J Thackham, J Ward, Z Zhang

Problem Description

Foot and Mouth Disease is of huge socio-economic importance, as well as the cause of significant animal suffering around the world. The virus, which is highly contagious, primarily infects epithelial (skin) cells in the mouth and on the feet, where symptoms are most easily seen (hence the name).

In the epithelium of the skin and tongue the virus rapidly replicates, killing the cell and resulting in vesicular lesions. Eventually the immune response tends to clear the virus from the system and these symptoms gradually disappear. In the epithelium of the soft palate, however, the virus replicates in a manner not fatal to the cells and can persist long after the animal has recovered. Such "carrier" animals present a risk in that, while perfectly healthy and potentially immune themselves, they could transmit the disease to other susceptible animals.

We wish to explore the potential mechanisms within epithelial cells which result in such dramatically different virus behaviour. These cells are fundamentally the same, and it is unclear as to which of the relatively minor differences might be responsible for the bifurcation in virus-cell dynamics. We hope that an intracellular model might indicate which aspects of the system are potentially responsible and thus help guide future experimental work.

Study Group Report

The epithelial cells in the two regions are fundamentally the same, yet the virus behaviour is dramatically different. The study group explored some of the potential mechanisms of the cell–virus dynamics that might be the cause of the different behaviour using mathematical modelling techniques. We are able to conclude that it may be the difference in epithelium thickness and susceptibility of the different layers of cells within the epithelium that is causing the observed differences of the virus in the palate and foot/tongue.

Download the full report

Follow-Up Activities

The following publications have been written as a result of this problem:

Modelling foot-and-mouth disease virus dynamics in oral epithelium to help identify the determinants of lysis
D Schley, J Ward, & Z Zhang (2011)
Bulletin of Mathematical Biology 73 (7), 1503–1528.

The following funding for further work has been obtained to investigate aspects of this problem:

Mathematical Modelling of the Potential Determinants of Foot-and-Mouth Disease Virus Induced Lysis of Bovine Epithelial Cells
J Ward
Biotechnology and Biological Sciences Research Council, four-year funded studentship, October 2008 to September 2012.