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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.

Giorgakoudi K, Gubbins S, Ward J, Juleff N, Zhang Z, Schley D - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: The Pirbright Institute, Pirbright, Surrey, United Kingdom; Department of Mathematical Sciences, Loughborough University, Loughborough, Leicestershire, United Kingdom.

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.

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Related in: MedlinePlus

Sensitivity analysis for alterations to viral replication parameter estimates.Model sensitivity to alterations of the estimates of the maximal replication rate of FMDV, ξ, and the rate of intracellular resource consumption by FMDV, ρ, as exhibited by the percentage of the remaining cellular space fraction, Sc, 48 hours post infection. (a), (b) Percentage of minimum surviving cellular space fraction over the whole tissue column for the case of DSP and tongue respectively. (c), (d) Percentage of average surviving cellular space fraction over the whole tissue column for the case of DSP and tongue respectively.
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pone.0138571.g006: Sensitivity analysis for alterations to viral replication parameter estimates.Model sensitivity to alterations of the estimates of the maximal replication rate of FMDV, ξ, and the rate of intracellular resource consumption by FMDV, ρ, as exhibited by the percentage of the remaining cellular space fraction, Sc, 48 hours post infection. (a), (b) Percentage of minimum surviving cellular space fraction over the whole tissue column for the case of DSP and tongue respectively. (c), (d) Percentage of average surviving cellular space fraction over the whole tissue column for the case of DSP and tongue respectively.

Mentions: Further exploration of the system with respect to the combined effect of these two parameters is presented in Fig 6. Values of the two parameters for which there is a different behaviour of the system between the two tissues in regards to the levels of cell survival can be identified, but the results are highly sensitive to small changes to these values.


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

Giorgakoudi K, Gubbins S, Ward J, Juleff N, Zhang Z, Schley D - PLoS ONE (2015)

Sensitivity analysis for alterations to viral replication parameter estimates.Model sensitivity to alterations of the estimates of the maximal replication rate of FMDV, ξ, and the rate of intracellular resource consumption by FMDV, ρ, as exhibited by the percentage of the remaining cellular space fraction, Sc, 48 hours post infection. (a), (b) Percentage of minimum surviving cellular space fraction over the whole tissue column for the case of DSP and tongue respectively. (c), (d) Percentage of average surviving cellular space fraction over the whole tissue column for the case of DSP and tongue respectively.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4592007&req=5

pone.0138571.g006: Sensitivity analysis for alterations to viral replication parameter estimates.Model sensitivity to alterations of the estimates of the maximal replication rate of FMDV, ξ, and the rate of intracellular resource consumption by FMDV, ρ, as exhibited by the percentage of the remaining cellular space fraction, Sc, 48 hours post infection. (a), (b) Percentage of minimum surviving cellular space fraction over the whole tissue column for the case of DSP and tongue respectively. (c), (d) Percentage of average surviving cellular space fraction over the whole tissue column for the case of DSP and tongue respectively.
Mentions: Further exploration of the system with respect to the combined effect of these two parameters is presented in Fig 6. Values of the two parameters for which there is a different behaviour of the system between the two tissues in regards to the levels of cell survival can be identified, but the results are highly sensitive to small changes to these values.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: The Pirbright Institute, Pirbright, Surrey, United Kingdom; Department of Mathematical Sciences, Loughborough University, Loughborough, Leicestershire, United Kingdom.

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.

No MeSH data available.


Related in: MedlinePlus