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

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Giorgakoudi, Kyriaki ; Gubbins, Simon ; Ward, John ; Juleff, Nicholas ; Zhang, Zhidong ; Schley, David (2015)

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. This work was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) [grant code: BBS/E/I/00001397], The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This is the final version of the article. It first appeared from PLoS via
  • References (33)
    33 references, page 1 of 4

    1. Grubman MJ, Baxt B. Foot-and-mouth disease. Clin Microbiol Rev. 2004; 17: 465-493. doi: 10.1128/ CMR.17.2.465-493.2004 PMID: 15084510

    2. Canadian Food Inspection Agency. Foot-and-Mouth Disease Hazard Specific Plan [Internet]. 2012; Available: Accessed 26 April 2012.

    3. South-East Asian FMD programme (SEAFMD). SEAFMD 2020. A roadmap for foot-and-mouth disease freedom with vaccination by 2020 in South-East Asia [Internet]. 2007; Available: http://www.seafmdrcu. Accessed 9 April 2010.

    4. Thompson D, Muriel P, Russell D, Osborne P, Bromley A, Rowland M, et al. Economic costs of the foot and mouth disease outbreak in the United Kingdom in 2001. Rev Sci Tech. 2002; 21: 675-687. PMID: 12523706

    5. Alexandersen S, Zhang Z, Donaldson AI, Garland AJM. The pathogenesis and diagnosis of foot-andmouth disease. J Comp Pathol. 2003; 129: 1-36. doi: 10.1016/S0021-9975(03)00041-0 PMID: 12859905

    6. Arzt J, Pacheco JM, Rodriguez LL. The early pathogenesis of foot-and-mouth disease in cattle after aerosol inoculation: identification of the nasopharynx as the primary site of infection. Vet Pathol. 2010; 47: 1048-1063. doi: 10.1177/0300985810372509 PMID: 20587691

    7. Young B, Heath JW. Wheater's Functional Histology. 4th ed. Edinburgh: Churchill Livingstone/Elsevier; 2000.

    8. Schley D, Ward J, Zhang Z. Modelling foot-and-mouth disease virus dynamics in oral epithelium to help identify the determinants of lysis. Bull Math Biol. 2011; 73: 1503-1529. doi: 10.1007/s11538-010- 9576-6 PMID: 20725794

    9. Monaghan P, Gold S, Simpson J, Zhang Z, Weinreb PH, Violette SM, et al. The αvβ6 integrin receptor for foot-and-mouth disease virus is expressed constitutively on the epithelial cells targeted in cattle. J Gen Virol. 2005; 86: 2769-2780. doi: 10.1099/vir.0.81172-0 PMID: 16186231

    10. Grubman MJ, Moraes MP, Diaz-San Segundo F, Pena L, De Los Santos T. Evading the host immune response: how foot-and-mouth disease virus has become an effective pathogen FEMS Immunol Med Microbiol. 2008; 53: 8-17. PMID: 18400012

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