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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.

No MeSH data available.


Related in: MedlinePlus

Simulation results for DSP and tongue over a 48 hour timescale.Epithelium surface used as the viral entry point for DSP and basement membrane as the viral entry point for tongue. (a), (b) Cellular space fraction, Sc, of DSP and tongue respectively. (c), (d) Intracellular viral load, VcSc, of DSP and tongue respectively measured in PFU/cm. (e), (f) Extracellular viral load, VeSe, of DSP and tongue respectively measured in PFU/cm. Green area at the bottom right hand corner of (e) indicates viral entry in DSP. Due to different scaling of (f), viral entry in tongue is not visible (bottom left hand corner). (g), (h) Intracellular resource, K, of DSP and tongue respectively, measured in cm−1. (i), (j) Activator concentration, E, of DSP and tongue respectively.
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pone.0138571.g004: Simulation results for DSP and tongue over a 48 hour timescale.Epithelium surface used as the viral entry point for DSP and basement membrane as the viral entry point for tongue. (a), (b) Cellular space fraction, Sc, of DSP and tongue respectively. (c), (d) Intracellular viral load, VcSc, of DSP and tongue respectively measured in PFU/cm. (e), (f) Extracellular viral load, VeSe, of DSP and tongue respectively measured in PFU/cm. Green area at the bottom right hand corner of (e) indicates viral entry in DSP. Due to different scaling of (f), viral entry in tongue is not visible (bottom left hand corner). (g), (h) Intracellular resource, K, of DSP and tongue respectively, measured in cm−1. (i), (j) Activator concentration, E, of DSP and tongue respectively.

Mentions: The model was investigated numerically for both DSP and tongue using the default parameter values (Table 2). All four entry points tested (see Table 3) had similar effects on the behaviour of the system: fast and complete destruction of the intracellular resource, K, and of the cellular fraction, Sc, and the presence of intracellular virus, Vc, and extracellular virus, Ve, in the tissue. In Fig 4 results of the cases corresponding to the most likely source of infection for each tissue are presented; DSP is a site of primary infection with FMDV [5] thus ep = LP, and tongue is usually infected through viraemia [5] so here ep = 0. These results are independent of the differences in epithelial tissue thickness with no signs of surviving cellular fraction when tongue thickness, LT, is reduced to the thickness of DSP, or DSP thickness, LP, increased to the size of tongue.


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)

Simulation results for DSP and tongue over a 48 hour timescale.Epithelium surface used as the viral entry point for DSP and basement membrane as the viral entry point for tongue. (a), (b) Cellular space fraction, Sc, of DSP and tongue respectively. (c), (d) Intracellular viral load, VcSc, of DSP and tongue respectively measured in PFU/cm. (e), (f) Extracellular viral load, VeSe, of DSP and tongue respectively measured in PFU/cm. Green area at the bottom right hand corner of (e) indicates viral entry in DSP. Due to different scaling of (f), viral entry in tongue is not visible (bottom left hand corner). (g), (h) Intracellular resource, K, of DSP and tongue respectively, measured in cm−1. (i), (j) Activator concentration, E, of DSP and tongue respectively.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0138571.g004: Simulation results for DSP and tongue over a 48 hour timescale.Epithelium surface used as the viral entry point for DSP and basement membrane as the viral entry point for tongue. (a), (b) Cellular space fraction, Sc, of DSP and tongue respectively. (c), (d) Intracellular viral load, VcSc, of DSP and tongue respectively measured in PFU/cm. (e), (f) Extracellular viral load, VeSe, of DSP and tongue respectively measured in PFU/cm. Green area at the bottom right hand corner of (e) indicates viral entry in DSP. Due to different scaling of (f), viral entry in tongue is not visible (bottom left hand corner). (g), (h) Intracellular resource, K, of DSP and tongue respectively, measured in cm−1. (i), (j) Activator concentration, E, of DSP and tongue respectively.
Mentions: The model was investigated numerically for both DSP and tongue using the default parameter values (Table 2). All four entry points tested (see Table 3) had similar effects on the behaviour of the system: fast and complete destruction of the intracellular resource, K, and of the cellular fraction, Sc, and the presence of intracellular virus, Vc, and extracellular virus, Ve, in the tissue. In Fig 4 results of the cases corresponding to the most likely source of infection for each tissue are presented; DSP is a site of primary infection with FMDV [5] thus ep = LP, and tongue is usually infected through viraemia [5] so here ep = 0. These results are independent of the differences in epithelial tissue thickness with no signs of surviving cellular fraction when tongue thickness, LT, is reduced to the thickness of DSP, or DSP thickness, LP, increased to the size of tongue.

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