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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 different viral entry points.Simulation results of cellular space fraction, Sc, for DSP and tongue over a 48 hour timescale for maximal replication rate, ξ, and rate of FMDV resource consumption, ρ, both set at 0.29 × their default estimates. (a), (b) Basement membrane used as the viral entry point for DSP and epithelium surface as the viral entry point for tongue respectively. (c), (d) Viral entry point for both DSP and tongue set at Li−3 × 10−3 cm. (e), (f) Viral entry point for both DSP and tongue set at 3 × 10−3 cm.
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pone.0138571.g007: Simulation results for different viral entry points.Simulation results of cellular space fraction, Sc, for DSP and tongue over a 48 hour timescale for maximal replication rate, ξ, and rate of FMDV resource consumption, ρ, both set at 0.29 × their default estimates. (a), (b) Basement membrane used as the viral entry point for DSP and epithelium surface as the viral entry point for tongue respectively. (c), (d) Viral entry point for both DSP and tongue set at Li−3 × 10−3 cm. (e), (f) Viral entry point for both DSP and tongue set at 3 × 10−3 cm.

Mentions: Setting the level of the maximal replication rate, ξ, and the level of resource consumption by FMDV, ρ, at 0.29 × their default estimates, we explored the effect of the site of viral entry to the epithelium (Fig 7). DSP exhibits higher levels of cell survival than tongue for all cases. Comparing the lowest level of cell survival for DSP, which is the result of viral entry at a point at about two cells distance from the basement membrane, with the highest level of tongue survival which is a result of viral entry at the basement membrane, there is still more cell survival in the DSP. For both tissues, higher levels of survival are observed for the default viral entry points, while interestingly the lowest levels of cell survival for the tongue are exhibited when FMDV enters on the granular layer surface or about two cells in from there.


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 different viral entry points.Simulation results of cellular space fraction, Sc, for DSP and tongue over a 48 hour timescale for maximal replication rate, ξ, and rate of FMDV resource consumption, ρ, both set at 0.29 × their default estimates. (a), (b) Basement membrane used as the viral entry point for DSP and epithelium surface as the viral entry point for tongue respectively. (c), (d) Viral entry point for both DSP and tongue set at Li−3 × 10−3 cm. (e), (f) Viral entry point for both DSP and tongue set at 3 × 10−3 cm.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0138571.g007: Simulation results for different viral entry points.Simulation results of cellular space fraction, Sc, for DSP and tongue over a 48 hour timescale for maximal replication rate, ξ, and rate of FMDV resource consumption, ρ, both set at 0.29 × their default estimates. (a), (b) Basement membrane used as the viral entry point for DSP and epithelium surface as the viral entry point for tongue respectively. (c), (d) Viral entry point for both DSP and tongue set at Li−3 × 10−3 cm. (e), (f) Viral entry point for both DSP and tongue set at 3 × 10−3 cm.
Mentions: Setting the level of the maximal replication rate, ξ, and the level of resource consumption by FMDV, ρ, at 0.29 × their default estimates, we explored the effect of the site of viral entry to the epithelium (Fig 7). DSP exhibits higher levels of cell survival than tongue for all cases. Comparing the lowest level of cell survival for DSP, which is the result of viral entry at a point at about two cells distance from the basement membrane, with the highest level of tongue survival which is a result of viral entry at the basement membrane, there is still more cell survival in the DSP. For both tissues, higher levels of survival are observed for the default viral entry points, while interestingly the lowest levels of cell survival for the tongue are exhibited when FMDV enters on the granular layer surface or about two cells in from there.

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