Bovine papillomavirus gene expression and inflammatory pathway activation vary between equine sarcoid tumour subtypes.
Abstract: Equine sarcoids are common non-metastasising skin tumours in horses, associated with bovine papillomavirus (BPV) infection. Six subtypes are recognised (occult, verrucose, nodular, fibroblastic, mixed and malevolent lesions), with variable clinical behaviour. The pathophysiology underlying varying tumour phenotype is poorly understood, and previous data on associations with viral load have been conflicting. To better understand this clinical variation, we investigated associations between tumour subtype and viral load, viral early protein gene expression, and expression of 10 host genes by quantitative polymerase chain reaction in 27 sarcoids and 5 normal skin samples. Viral DNA copy number did not differ between subtypes but was significantly higher in animals with fewer tumours. Expression of BPV E2 and E6 was higher in occult lesions compared to fibroblastic or nodular lesions, while E5 expression was higher in previously-treated lesions. Of the host genes, only IL6 and IL1B differed between subtypes, with higher expression in fibroblastic lesions, while IL10 and CCL5 were elevated compared to skin in all lesion types, and elevations in TNF and TGFB1 were significant for occult lesions only. Expression of TLR9, ATR, VEGFA and PTGS2 in sarcoids was not significantly different from normal skin, suggesting differences between BPV and human papillomavirus tumorigenesis. Results for BPV viral load and gene expression differed from previous reports and are insufficient to explain the spectrum of tumour phenotypes. Activation of both pro-inflammatory and anti-inflammatory immune pathways in sarcoids could influence tumour growth and effective immune responses, and the contribution of specific infiltrating immune cells requires further investigation.
Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.
Publication Date: 2024-10-01 PubMed ID: 39357074DOI: 10.1016/j.vetimm.2024.110838Google Scholar: Lookup
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Summary
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The research team explored the variations in bovine papillomavirus gene expression and inflammatory pathway activation across different types of equine sarcoid skin tumours. They discovered differences across tumour types but found that the viral load and gene expression data were not sufficient to explain the diverse tumour characteristics.
Research Context and Aims
- Sarcoids are prevalent skin tumours in horses that are non-metastasising and associated with bovine papillomavirus (BPV) infection.
- These tumours come in six different subtypes, each exhibiting variable clinical behaviour.
- However, very little is understood about the pathophysiology causing the differences in tumour phenotype, and existing data on viral load associations have had conflicting results.
- To dig deeper into these clinical variations, the researchers investigated correlations between tumour subtype, viral load, expression of early protein genes in the virus, and expression of 10 host genes.
Research Methodology
- The research involved quantitative polymerase chain reaction (PCR) tests in 27 sarcoids and 5 normal skin samples.
Findings and Insights
- The research found no differences in viral DNA copy number between tumour types; however, it was noticeably higher in animals with fewer tumours.
- Expression of BPV proteins E2 and E6 was found higher in occult lesions compared to fibroblastic or nodular lesions.
- Lesions that were previously treated showed higher E5 expression levels.
- Among host genes, only IL6 and IL1B differed across tumour types, with fibroblastic lesions showing a higher expression, while IL10 and CCL5 were elevated compared to skin in all lesion types.
- Occult lesions exhibited significant elevations in TNF and TGFB1.
- The expression of TLR9, ATR, VEGFA and PTGS2 in sarcoids was not significantly different compared to normal skin, suggesting differences in tumorigenesis between BPV and human papillomavirus.
Interpretation of Findings and Future Directions
- The study established that viral load and gene expression findings vary from previous reports and aren’t sufficient to fully explain the range of tumour phenotypes.
- Activation of both pro-inflammatory and anti-inflammatory immune pathways in sarcoids could influence tumour growth and immune responses.
- The influence of specific infiltrating immune cells on these pathways is still unclear and should be the focus of future research.
Cite This Article
APA
Parkinson NJ, Ward A, Malbon AJ, Reardon RJM, Kelly PG.
(2024).
Bovine papillomavirus gene expression and inflammatory pathway activation vary between equine sarcoid tumour subtypes.
Vet Immunol Immunopathol, 277, 110838.
https://doi.org/10.1016/j.vetimm.2024.110838 Publication
Researcher Affiliations
- College of Medicine and Veterinary Medicine, University of Edinburgh, Royal (Dick) School of Veterinary Studies, University of Edinburgh, United Kingdom. Electronic address: nick.parkinson@ed.ac.uk.
- College of Medicine and Veterinary Medicine, University of Edinburgh, Royal (Dick) School of Veterinary Studies, University of Edinburgh, United Kingdom.
- College of Medicine and Veterinary Medicine, University of Edinburgh, Royal (Dick) School of Veterinary Studies, University of Edinburgh, United Kingdom.
- College of Medicine and Veterinary Medicine, University of Edinburgh, Royal (Dick) School of Veterinary Studies, University of Edinburgh, United Kingdom.
- College of Medicine and Veterinary Medicine, University of Edinburgh, Royal (Dick) School of Veterinary Studies, University of Edinburgh, United Kingdom.
Conflict of Interest Statement
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Citations
This article has been cited 2 times.- Alkayyal AA. Insights from veterinary models for advancing oncolytic virotherapy through comparative oncology. Front Mol Biosci 2025;12:1615393.
- Zhao Y, Zhao M, Zhang W. Identification of a novel papillomavirus in oral swabs from giant pandas (Ailuropoda melanoleuca). Front Vet Sci 2024;11:1457471.
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