p38 mitogen-activated protein kinase is crucial for bovine papillomavirus type-1 transformation of equine fibroblasts.
Abstract: Equine sarcoids represent the most common skin tumours in equids worldwide, characterized by extensive invasion and infiltration of lymphatics, rare regression and high recurrence after surgical intervention. Bovine papillomavirus type-1 (BPV-1) and less commonly BPV-2 are the causative agents of the diseases. It has been demonstrated that BPV-1 viral gene expression is necessary for maintaining the transformation phenotype. However, the underlying mechanism for BPV-1 transformation remains largely unknown, and the cellular factors involved in transformation are not fully understood. Previously mitogen-activated protein kinase (MAPK) signalling pathway has been shown to be important for cellular transformation. This study investigated the role of p38 MAPK (p38) in the transformation of equine fibroblasts by BPV-1. Elevated expression of phosphorylated p38 was observed in BPV-1 expressing fibroblasts due to the expression of BPV-1 E5 and E6. The phosphorylation of the MK2 kinase, a substrate of p38, was also enhanced. Inhibition of p38 activity by its selective inhibitor SB203580 changed cell morphology, reduced the proliferation of sarcoid fibroblasts and inhibited cellular invasiveness, indicating the indispensable role of p38 in BPV-1 transformation of equine fibroblasts. These findings provide new insights into the pathogenesis of equine sarcoids and suggest that p38 could be a potential target for equine sarcoid therapy.
Publication Date: 2011-04-06 PubMed ID: 21471309DOI: 10.1099/vir.0.031526-0Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article explores the role p38 mitogen-activated protein kinase plays in the transformation of horse fibroblasts caused by bovine papillomavirus type-1. This finding can aid in understanding the pathogenesis of equine sarcoids and could potentially form the basis for new treatment strategies.
Background
- The study revolves around equine sarcoids, the most common skin tumours in equids globally. These tumours are characterized by extensive invasion, infiltration of lymphatics, rare regression, and a high recurrence rate after surgery.
- The causative agents of such diseases are mainly BPV-1 and less frequently, BPV-2. It has been established that BPV-1 viral gene expression is crucial for maintaining the transformation phenotype, but the transformation mechanism and the cellular factors involved are not clearly understood.
- The study focuses on MAPK (mitogen-activated protein kinase) signalling pathway, which has previously been shown to have a significant role in cellular transformation.
The Role of p38 MAPK in BPV-1 Transformation
- In this research, the investigators studied the role of p38 MAPK (p38) in the transformation of equine fibroblasts by BPV-1. It was observed that the expression of phosphorylated p38 was elevated in fibroblasts expressing BPV-1 due to BPV-1 E5 and E6 expression.
- Another finding was that the phosphorylation of the MK2 kinase, which is a substrate of p38, was also enhanced.
The Effects of Inhibiting p38 Activity
- To explore the role of p38 further, the researchers inhibited its activity using a selective inhibitor SB203580. This led to changes in cell morphology, reduced proliferation of sarcoid fibroblasts, and inhibited cellular invasiveness.
- This indicates the indispensable role of p38 in BPV-1’s transformation of equine fibroblasts.
Implications of the Study
- The study’s findings provide new insights into the development of equine sarcoids.
- P38 potentially represents a new target for treating equine sarcoids, indicating potential therapeutic applications based on this research.
Cite This Article
APA
Yuan Z, Gault EA, Campo MS, Nasir L.
(2011).
p38 mitogen-activated protein kinase is crucial for bovine papillomavirus type-1 transformation of equine fibroblasts.
J Gen Virol, 92(Pt 8), 1778-1786.
https://doi.org/10.1099/vir.0.031526-0 Publication
Researcher Affiliations
- Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Campus, Bearsden Road, Glasgow G61 1QH, UK.
- Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Campus, Bearsden Road, Glasgow G61 1QH, UK.
- Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Campus, Bearsden Road, Glasgow G61 1QH, UK.
- Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Campus, Bearsden Road, Glasgow G61 1QH, UK.
MeSH Terms
- Animals
- Bovine papillomavirus 1 / genetics
- Bovine papillomavirus 1 / physiology
- Cell Line, Tumor
- Cell Transformation, Viral
- Fibroblasts / enzymology
- Fibroblasts / virology
- Horse Diseases / enzymology
- Horse Diseases / virology
- Horses
- Papillomavirus Infections / enzymology
- Papillomavirus Infections / veterinary
- Papillomavirus Infections / virology
- Phosphorylation
- Skin Neoplasms / enzymology
- Skin Neoplasms / veterinary
- Skin Neoplasms / virology
- p38 Mitogen-Activated Protein Kinases / genetics
- p38 Mitogen-Activated Protein Kinases / metabolism
Citations
This article has been cited 3 times.- DiMaio D, Petti LM. The E5 proteins. Virology 2013 Oct;445(1-2):99-114.
- Finlay M, Yuan Z, Morgan IM, Campo MS, Nasir L. Equine sarcoids: Bovine Papillomavirus type 1 transformed fibroblasts are sensitive to cisplatin and UVB induced apoptosis and show aberrant expression of p53. Vet Res 2012 Dec 4;43(1):81.
- Karalus W, Subharat S, Orbell G, Vaatstra B, Munday JS. Equine sarcoids: A clinicopathologic study of 49 cases, with mitotic count and clinical type predictive of recurrence. Vet Pathol 2024 May;61(3):357-365.
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