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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

Schematic diagram of the continuum model.Example of FMDV infection of tongue epithelial cells with virus entering through the basement membrane. Darker shades of green and purple indicate higher concentration of extracellular and cellular FMDV respectively. Infection dynamics are the same in DSP, though tissue structure and usual site of viral entry are different. Tongue epithelium thickness is LT, basal-spinous epithelium thickness is LTg, while basal cell layer thickness is LTb (left hand side). For DSP the equivalents are LP for epithelium thickness and LPb for basal cell layer thickness. No granular layer is present in DSP, therefore there is no distinction between whole epithelium and basal-spinous epithelium thickness. Function gB (red line, right hand side) takes values of approximately 1 for basal cells, dropping to approximately zero everywhere else. Function gG (black dashed line) is approximately 1 for the basal-spinous epithelium, dropping to approximately zero for granular cells.
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pone.0138571.g003: Schematic diagram of the continuum model.Example of FMDV infection of tongue epithelial cells with virus entering through the basement membrane. Darker shades of green and purple indicate higher concentration of extracellular and cellular FMDV respectively. Infection dynamics are the same in DSP, though tissue structure and usual site of viral entry are different. Tongue epithelium thickness is LT, basal-spinous epithelium thickness is LTg, while basal cell layer thickness is LTb (left hand side). For DSP the equivalents are LP for epithelium thickness and LPb for basal cell layer thickness. No granular layer is present in DSP, therefore there is no distinction between whole epithelium and basal-spinous epithelium thickness. Function gB (red line, right hand side) takes values of approximately 1 for basal cells, dropping to approximately zero everywhere else. Function gG (black dashed line) is approximately 1 for the basal-spinous epithelium, dropping to approximately zero for granular cells.

Mentions: A mathematical model was developed to investigate the potential determinants of FMDV lysis. The model is aimed at investigating the spread, cell infiltration and cell lysis by virions introduced into epithelial tissue. As events occur over space and time, the model is formulated in terms of a system of linked nonlinear partial differential equations (PDEs). For simplicity, the model describes the dynamics of FMDV in a column of epithelium, so that there is only one spatial dimension (Fig 3). Moreover, the model only considers the dynamics of FMDV in epithelium over the short-term (approximately 48 hours), for a timescale sufficient for lesions to occur but before the adaptive immune response begins to play a significant role. Model variables are presented in Table 1. Taking an Occam’s razor approach, it is assumed that cells in the DSP and tongue are fundamentally the same, with the exception of already described structural differences between the two tissues.


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)

Schematic diagram of the continuum model.Example of FMDV infection of tongue epithelial cells with virus entering through the basement membrane. Darker shades of green and purple indicate higher concentration of extracellular and cellular FMDV respectively. Infection dynamics are the same in DSP, though tissue structure and usual site of viral entry are different. Tongue epithelium thickness is LT, basal-spinous epithelium thickness is LTg, while basal cell layer thickness is LTb (left hand side). For DSP the equivalents are LP for epithelium thickness and LPb for basal cell layer thickness. No granular layer is present in DSP, therefore there is no distinction between whole epithelium and basal-spinous epithelium thickness. Function gB (red line, right hand side) takes values of approximately 1 for basal cells, dropping to approximately zero everywhere else. Function gG (black dashed line) is approximately 1 for the basal-spinous epithelium, dropping to approximately zero for granular cells.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4592007&req=5

pone.0138571.g003: Schematic diagram of the continuum model.Example of FMDV infection of tongue epithelial cells with virus entering through the basement membrane. Darker shades of green and purple indicate higher concentration of extracellular and cellular FMDV respectively. Infection dynamics are the same in DSP, though tissue structure and usual site of viral entry are different. Tongue epithelium thickness is LT, basal-spinous epithelium thickness is LTg, while basal cell layer thickness is LTb (left hand side). For DSP the equivalents are LP for epithelium thickness and LPb for basal cell layer thickness. No granular layer is present in DSP, therefore there is no distinction between whole epithelium and basal-spinous epithelium thickness. Function gB (red line, right hand side) takes values of approximately 1 for basal cells, dropping to approximately zero everywhere else. Function gG (black dashed line) is approximately 1 for the basal-spinous epithelium, dropping to approximately zero for granular cells.
Mentions: A mathematical model was developed to investigate the potential determinants of FMDV lysis. The model is aimed at investigating the spread, cell infiltration and cell lysis by virions introduced into epithelial tissue. As events occur over space and time, the model is formulated in terms of a system of linked nonlinear partial differential equations (PDEs). For simplicity, the model describes the dynamics of FMDV in a column of epithelium, so that there is only one spatial dimension (Fig 3). Moreover, the model only considers the dynamics of FMDV in epithelium over the short-term (approximately 48 hours), for a timescale sufficient for lesions to occur but before the adaptive immune response begins to play a significant role. Model variables are presented in Table 1. Taking an Occam’s razor approach, it is assumed that cells in the DSP and tongue are fundamentally the same, with the exception of already described structural differences between the two tissues.

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