title: Using Mathematical Modelling to Explore Hypotheses about the Role of Bovine Epithelium Structure in Foot-And-Mouth Disease Virus-Induced Cell Lysis.
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.
authors.affiliation: The Pirbright Institute, Pirbright, Surrey, United Kingdom; Department of Mathematical Sciences, Loughborough University, Loughborough, Leicestershire, United Kingdom.
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Giorgakoudi
authors.affiliation: The Pirbright Institute, Pirbright, Surrey, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Gubbins
authors.affiliation: Department of Mathematical Sciences, Loughborough University, Loughborough, Leicestershire, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Ward
authors.affiliation: The Pirbright Institute, Pirbright, Surrey, United Kingdom.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Juleff
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: The Pirbright Institute, Pirbright, Surrey, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Schley
mesh_terms: D000818:Animals; D002417:Cattle; D004848:Epithelium / Q000473:pathology / Q000821:virology*; D029544:Foot-and-Mouth Disease Virus / Q000472:pathogenicity* / Q000502:physiology; D008962:Models, Theoretical; D014779:Virus Replication