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Using Mathematical Modelling to Explore Hypotheses about the Role of Bovine Epithelium Structure in Foot-And-Mouth Disease Virus-Induced Cell Lysis.


Type

Article

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Authors

Giorgakoudi, Kyriaki 
Gubbins, Simon 
Ward, John 
Juleff, Nicholas 
Zhang, Zhidong 

Abstract

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals. FMD virus (FMDV) shows a strong tropism for epithelial cells, and FMD is characterised by cell lysis and the development of vesicular lesions in certain epithelial tissues (for example, the tongue). By contrast, other epithelial tissues do not develop lesions, despite being sites of viral replication (for example, the dorsal soft palate). The reasons for this difference are poorly understood, but hypotheses are difficult to test experimentally. In order to identify the factors which drive cell lysis, and consequently determine the development of lesions, we developed a partial differential equation model of FMDV infection in bovine epithelial tissues and used it to explore a range of hypotheses about epithelium structure which could be driving differences in lytic behaviour observed in different tissues. Our results demonstrate that, based on current parameter estimates, epithelial tissue thickness and cell layer structure are unlikely to be determinants of FMDV-induced cell lysis. However, differences in receptor distribution or viral replication amongst cell layers could influence the development of lesions, but only if viral replication rates are much lower than current estimates.

Description

Keywords

Animals, Cattle, Epithelium, Foot-and-Mouth Disease Virus, Models, Theoretical, Virus Replication

Journal Title

PLoS One

Conference Name

Journal ISSN

1932-6203
1932-6203

Volume Title

Publisher

Public Library of Science (PLoS)
Sponsorship
This work was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) [grant code: BBS/E/I/00001397], http://www.bbsrc.ac.uk/home/home.aspx. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.