Using mathematical modelling to explore hypotheses about the role of bovine epithelium structure in foot-and-mouth disease virus-induced cell lysis

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 di erence are poorly understood, but hypotheses are di cult to test experimentally. In order to identify the factors which drive cell lysis, and consequently determine the development of lesions, we developed a partial di erential 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 di erences in lytic behaviour observed in di erent 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, di erences in receptor distribution or viral replication amongst cell layers could in uence the development of lesions, but only if viral replication rates are much lower than current estimates.