Limits...
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

(a)–(d) Typical FMDV epithelial vesicles on the tongue and hoof of infected cattle (black arrows).(a) Recently ruptured tongue vesicle, lesion is extensive as demarcated by blanching of the epithelium across the rostral surface of the tongue. Blanched epithelium has begun to slough, leaving erosions. (b) Unruptured fluid filled vesicle on the heel of the hoof. (c) Erosion on the rostal tip of the tongue, epithelium has sloughed exposing raw epithelium below. (d) Ruptured interdigital vesicle, blanched epithelium is sloughing exposing raw epithelium below.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4592007&req=5

pone.0138571.g001: (a)–(d) Typical FMDV epithelial vesicles on the tongue and hoof of infected cattle (black arrows).(a) Recently ruptured tongue vesicle, lesion is extensive as demarcated by blanching of the epithelium across the rostral surface of the tongue. Blanched epithelium has begun to slough, leaving erosions. (b) Unruptured fluid filled vesicle on the heel of the hoof. (c) Erosion on the rostal tip of the tongue, epithelium has sloughed exposing raw epithelium below. (d) Ruptured interdigital vesicle, blanched epithelium is sloughing exposing raw epithelium below.

Mentions: The principal clinical signs of FMD are vesicular lesions on the feet and in or around the mouth (Fig 1); other clinical signs include oral or nasal discharge, lameness, reluctance to stand or move and fever [5]. The development of vesicular lesions is observed in certain epithelial tissues within infected animals, while other tissues remain unaffected. For example, although cattle develop severe vesicular lesions in the tongue [1], the epithelial layer on the dorsal surface of the soft palate (DSP) (see Fig 2) does not develop visible vesicles or lesions [5]; it is, however, not known whether cell death still occurs within the DSP. The absence of lesions in the DSP is despite the fact that this is considered to be a primary site of infection and one of the main sites of initial FMDV replication [5, 6]. The causes of the different pathological behaviour between the tongue and the DSP are currently unknown, but it has been suggested that it is a consequence of the different epithelial structure of these tissues [5].


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)

(a)–(d) Typical FMDV epithelial vesicles on the tongue and hoof of infected cattle (black arrows).(a) Recently ruptured tongue vesicle, lesion is extensive as demarcated by blanching of the epithelium across the rostral surface of the tongue. Blanched epithelium has begun to slough, leaving erosions. (b) Unruptured fluid filled vesicle on the heel of the hoof. (c) Erosion on the rostal tip of the tongue, epithelium has sloughed exposing raw epithelium below. (d) Ruptured interdigital vesicle, blanched epithelium is sloughing exposing raw epithelium below.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0138571.g001: (a)–(d) Typical FMDV epithelial vesicles on the tongue and hoof of infected cattle (black arrows).(a) Recently ruptured tongue vesicle, lesion is extensive as demarcated by blanching of the epithelium across the rostral surface of the tongue. Blanched epithelium has begun to slough, leaving erosions. (b) Unruptured fluid filled vesicle on the heel of the hoof. (c) Erosion on the rostal tip of the tongue, epithelium has sloughed exposing raw epithelium below. (d) Ruptured interdigital vesicle, blanched epithelium is sloughing exposing raw epithelium below.
Mentions: The principal clinical signs of FMD are vesicular lesions on the feet and in or around the mouth (Fig 1); other clinical signs include oral or nasal discharge, lameness, reluctance to stand or move and fever [5]. The development of vesicular lesions is observed in certain epithelial tissues within infected animals, while other tissues remain unaffected. For example, although cattle develop severe vesicular lesions in the tongue [1], the epithelial layer on the dorsal surface of the soft palate (DSP) (see Fig 2) does not develop visible vesicles or lesions [5]; it is, however, not known whether cell death still occurs within the DSP. The absence of lesions in the DSP is despite the fact that this is considered to be a primary site of infection and one of the main sites of initial FMDV replication [5, 6]. The causes of the different pathological behaviour between the tongue and the DSP are currently unknown, but it has been suggested that it is a consequence of the different epithelial structure of these tissues [5].

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