Bovine papillomavirus load and mRNA expression, cell proliferation and p53 expression in four clinical types of equine sarcoid.
Abstract: Equine sarcoids, the most common skin tumours in horses, are induced by bovine papillomavirus (BPV). Their clinical appearance varies from small stable patches to aggressively growing masses. Differences in BPV load and mRNA expression and Ki67 and p53 immunostaining among four clinical types (fibroblastic, occult, nodular and verrucous sarcoids) were evaluated to test the hypothesis that the clinical behaviour of equine sarcoids correlates with BPV activity. Viral load and expression of the BPV E2, E5, E6 and E7 genes were determined using quantitative real-time PCR. The proliferative fraction (PF) of the tumours was determined by Ki67 immunostaining and expression of p53 was analysed by immunohistochemistry. Nodular sarcoids showed a significantly higher viral load than the other types. A significant overall difference among the four types was observed for E2, E5, E6 and E7 mRNA expression. Nodular sarcoids showed the highest expression level for each BPV gene examined, followed by verrucous, fibroblastic and occult tumours. Viral DNA and mRNA outcomes correlated with each other, indicating a similar transcription pattern in each type of sarcoid. The PF was significantly higher in the superficial layers of verrucous and fibroblastic sarcoids compared with occult and nodular types. No significant difference was observed for the PF in the deep layers and for p53 expression. These results clearly demonstrate the omnipresence and active transcription of BPV in equine sarcoids. However, the hypothesis that the clinical behaviour of an equine sarcoid can be explained on the basis of differences in BPV activity could not be demonstrated.
Publication Date: 2007-07-12 PubMed ID: 17622617DOI: 10.1099/vir.0.82876-0Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research explored the relationship between the clinical behavior of equine skin tumors (sarcoids) and bovine papillomavirus (BPV) activity. The analysis included evaluation of BPV load, gene expression, and tumor cell proliferation across four different types of sarcoids. However, the study couldn’t conclusively link the clinical behavior of these horse skin tumors to BPV activity.
Methods and Objective
- The study aimed to investigate the relationships between sarcoid clinical types, BPV activity, and tumor development. It assessed four clinical types of equine sarcoids: fibroblastic, occult, nodular, and verrucous.
- The researchers hypothesized that the clinical behavior of these skin tumors could be based on differences in BPV activity. They thus compared the BPV load and mRNA expression, as well as cell proliferation and p53 expression (a protein related to cell cycle regulation and stability) across these sarcoid types.
Procedure
- BPV load and expression of its genes (E2, E5, E6, and E7) were determined using quantitative real-time polymerase chain reaction (PCR).
- The proliferative fraction (PF), a measure of the number of cells in the process of dividing, of the tumors was determined using Ki67 immunostaining, a common method to measure cell proliferation.
- p53 expression, indicative of if cells are responding to the stress of potential malignancy, was also analyzed.
Findings
- Nodular sarcoids had a significantly higher viral load in comparison to the other sarcoid types. They also showed the highest level of mRNA expression for each BPV gene examined.
- There was a significant overall variance in E2, E5, E6, and E7 mRNA expression among the four sarcoid types.
- The PF was notably higher in the superficial layers of verrucous and fibroblastic sarcoids compared to occult and nodular types. However, no significant difference was found for the PF in the deeper layers of the tumors or for p53 expression levels.
- The outcomes pertaining to viral DNA and mRNA synchronized, which indicates a similar transcription pattern for each sarcoid type.
Conclusion
- The study affirms the presence and active transcription of BPV in equine sarcoids.
- However, the researchers found no clear evidence to support their hypothesis that the clinical behavior of equine sarcoids can be explained on the basis of variations in BPV activity.
Cite This Article
APA
Bogaert L, Van Poucke M, De Baere C, Dewulf J, Peelman L, Ducatelle R, Gasthuys F, Martens A.
(2007).
Bovine papillomavirus load and mRNA expression, cell proliferation and p53 expression in four clinical types of equine sarcoid.
J Gen Virol, 88(Pt 8), 2155-2161.
https://doi.org/10.1099/vir.0.82876-0 Publication
Researcher Affiliations
- Ghent University, Faculty of Veterinary Medicine, Department of Surgery and Anaesthesiology of Domestic Animals, Salisburylaan 133, B-9820 Merelbeke, Belgium.
- Ghent University, Faculty of Veterinary Medicine, Department of Nutrition, Genetics and Ethology, Heidestraat 19, B-9820 Merelbeke, Belgium.
- Ghent University, Faculty of Veterinary Medicine, Department of Surgery and Anaesthesiology of Domestic Animals, Salisburylaan 133, B-9820 Merelbeke, Belgium.
- Ghent University, Faculty of Veterinary Medicine, Department of Obstetrics, Reproduction and Herd Health, Salisburylaan 133, B-9820 Merelbeke, Belgium.
- Ghent University, Faculty of Veterinary Medicine, Department of Nutrition, Genetics and Ethology, Heidestraat 19, B-9820 Merelbeke, Belgium.
- Ghent University, Faculty of Veterinary Medicine, Department of Pathology, Bacteriology and Avian Diseases, Salisburylaan 133, B-9820 Merelbeke, Belgium.
- Ghent University, Faculty of Veterinary Medicine, Department of Surgery and Anaesthesiology of Domestic Animals, Salisburylaan 133, B-9820 Merelbeke, Belgium.
- Ghent University, Faculty of Veterinary Medicine, Department of Surgery and Anaesthesiology of Domestic Animals, Salisburylaan 133, B-9820 Merelbeke, Belgium.
MeSH Terms
- Animals
- Bovine papillomavirus 1 / genetics
- Bovine papillomavirus 1 / isolation & purification
- DNA, Viral / genetics
- DNA-Binding Proteins / genetics
- Diagnosis, Differential
- Horse Diseases / diagnosis
- Horse Diseases / metabolism
- Horse Diseases / virology
- Horses / virology
- Immunohistochemistry
- Ki-67 Antigen / analysis
- Ki-67 Antigen / metabolism
- Male
- Oncogene Proteins, Viral / genetics
- Papillomavirus Infections / diagnosis
- Papillomavirus Infections / metabolism
- Papillomavirus Infections / veterinary
- Papillomavirus Infections / virology
- Polymerase Chain Reaction
- RNA, Messenger / analysis
- RNA, Viral / analysis
- Skin / metabolism
- Skin / virology
- Skin Neoplasms / diagnosis
- Skin Neoplasms / metabolism
- Skin Neoplasms / veterinary
- Skin Neoplasms / virology
- Tumor Suppressor Protein p53 / analysis
- Tumor Suppressor Protein p53 / metabolism
- Viral Proteins / genetics
Citations
This article has been cited 16 times.- Hainisch EK, Jindra C, Reicher P, Miglinci L, Brodesser DM, Brandt S. Bovine Papillomavirus Type 1 or 2 Virion-Infected Primary Fibroblasts Constitute a Near-Natural Equine Sarcoid Model.. Viruses 2022 Nov 28;14(12).
- Pawlina-Tyszko K, Semik-Gurgul E, Ząbek T, Witkowski M. Methylation Status of Gene Bodies of Selected microRNA Genes Associated with Neoplastic Transformation in Equine Sarcoids.. Cells 2022 Jun 14;11(12).
- Gysens L, Vanmechelen B, Haspeslagh M, Maes P, Martens A. New approach for genomic characterisation of equine sarcoid-derived BPV-1/-2 using nanopore-based sequencing.. Virol J 2022 Jan 6;19(1):8.
- Munday JS, Orbell G, Fairley RA, Hardcastle M, Vaatstra B. Evidence from a Series of 104 Equine Sarcoids Suggests That Most Sarcoids in New Zealand Are Caused by Bovine Papillomavirus Type 2, although Both BPV1 and BPV2 DNA Are Detectable in around 10% of Sarcoids.. Animals (Basel) 2021 Oct 29;11(11).
- Munday JS, Gedye K, Daudt C, Chaves Da Silva F. The Development of Novel Primer Sets to Specifically Amplify Each of the Five Different Deltapapillomaviruses That Cause Neoplasia after Cross-Species Infection.. Vet Sci 2021 Sep 26;8(10).
- Saied AA, Metwally AA, Mohamed HMA, Haridy MAM. The contribution of bovines to human health against viral infections.. Environ Sci Pollut Res Int 2021 Sep;28(34):46999-47023.
- Al-Salihi KA, Al-Dabhawi AH, Ajeel AA, Erzuki IA, Ali TAH. Clinico-Histopathological and Immunohistochemical Study of Ruminant's Cutaneous Papillomavirus in Iraq.. Vet Med Int 2020;2020:5691974.
- Unger L, Jagannathan V, Pacholewska A, Leeb T, Gerber V. Differences in miRNA differential expression in whole blood between horses with sarcoid regression and progression.. J Vet Intern Med 2019 Jan;33(1):241-250.
- Haspeslagh M, Jordana Garcia M, Vlaminck LEM, Martens AM. Topical use of 5% acyclovir cream for the treatment of occult and verrucous equine sarcoids: a double-blinded placebo-controlled study.. BMC Vet Res 2017 Oct 6;13(1):296.
- Wilson AD, Hicks C. Both tumour cells and infiltrating T-cells in equine sarcoids express FOXP3 associated with an immune-supressed cytokine microenvironment.. Vet Res 2016 May 9;47(1):55.
- Bogaert L, Woodham AW, Da Silva DM, Martens A, Meyer E, Kast WM. A novel murine model for evaluating bovine papillomavirus prophylactics/therapeutics for equine sarcoid-like tumours.. J Gen Virol 2015 Sep;96(9):2764-2768.
- Bocaneti F, Altamura G, Corteggio A, Velescu E, Borzacchiello G. Expression of bcl-2 and p53 in bovine cutaneous fibropapillomas.. Infect Agent Cancer 2015;10(1):2.
- Trewby H, Ayele G, Borzacchiello G, Brandt S, Campo MS, Del Fava C, Marais J, Leonardi L, Vanselow B, Biek R, Nasir L. Analysis of the long control region of bovine papillomavirus type 1 associated with sarcoids in equine hosts indicates multiple cross-species transmission events and phylogeographical structure.. J Gen Virol 2014 Dec;95(Pt 12):2748-2756.
- Corteggio A, Altamura G, Roperto F, Borzacchiello G. Bovine papillomavirus E5 and E7 oncoproteins in naturally occurring tumors: are two better than one?. Infect Agent Cancer 2013 Jan 9;8(1):1.
- 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.
- Yuan ZQ, Nicolson L, Marchetti B, Gault EA, Campo MS, Nasir L. Transcriptional changes induced by bovine papillomavirus type 1 in equine fibroblasts.. J Virol 2008 Jul;82(13):6481-91.
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