Different contribution of bovine papillomavirus type 1 oncoproteins to the transformation of equine fibroblasts.
Abstract: Equine sarcoids represent the most common skin tumours in equids worldwide, characterized by localized invasion, rare regression and high recurrence following surgical intervention. Bovine papillomavirus type 1 (BPV-1) and less commonly BPV-2 are now widely recognized as the causative agents of the disease. Fibroblasts isolated from sarcoids are highly invasive. Invasion is associated with a high level of viral gene expression and matrix metalloproteinase upregulation. However, it remains unclear to what extent BPV-1 proteins are involved in the transformation of equine cells. To address this question, the individual viral genes E5, E6 and E7 were overexpressed in normal equine fibroblasts (EqPalF cells) and in the immortal but not fully transformed sarcoid-derived EqS02a cell line. The proliferation and invasiveness of these cell lines were assessed. E5 and E6 were found to be responsible for the enhanced cell proliferation and induction of increased invasion in EqS02a cells, whilst E7 appeared to enhance cell anchorage independence. Knockdown of BPV-1 oncogene expression by small interfering RNA reversed the transformed phenotype of sarcoid fibroblasts. Together, these observations strongly suggest that BPV-1 proteins play indispensable roles in the transformation of equine fibroblasts. These data also suggest that BPV-1 proteins are potential drug targets for equine sarcoid therapy.
Publication Date: 2010-12-22 PubMed ID: 21177927DOI: 10.1099/vir.0.028191-0Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research investigates how specific proteins in Bovine Papillomavirus Type 1 (BPV-1) influence the transformation of normal horse cells into highly invasive cancerous cells, known as equine sarcoids.
Background
- The study looks into the disease known as equine sarcoids, which are some of the most prevalent skin tumors in horses and are typically very invasive and recurrent even after surgical treatment.
- Equine sarcoids are largely caused by BPV-1 and also, but less frequently, by BPV-2. Fibroblasts isolated from these tumors exhibit high invasiveness and significant upregulation of matrix metalloproteinase, linked to increased viral gene expression.
- Prior to this study, it was unclear which specific proteins in the BPV-1 virus were responsible for transforming healthy cells into cancerous cells. This transformation is central to the development of equine sarcoids.
Methodology
- The research involved overexpressing individual viral genes E5, E6, and E7 in normal equine fibroblasts (EqPalF cells) and the not fully transformed but immortal sarcoid-derived EqS02a cell line.
- This experiment was used to assess the roles of these genes in the cell proliferation and invasiveness of these cell lines. Researchers also used small interfering RNA to knock down the expression of BPV-1 oncogenes and observe the effects on the fibroblasts.
Findings
- E5 and E6 genes were found to contribute to increased cell growth and invasion in EqS02a cells. E7, on the other hand, seemed to enhance the cells’ anchorage independence.
- When the BPV-1 oncogene expression was interrupted by the small interfering RNA, the fibroblasts reverted back from their transformed (cancerous) state.
- Consequently, these observations strongly suggest that BPV-1 proteins play crucial roles in the transformation of equine fibroblasts. This implies that they may also be potential targets for treating equine sarcoids in a drug therapy context.
Cite This Article
APA
Yuan Z, Gault EA, Campo MS, Nasir L.
(2010).
Different contribution of bovine papillomavirus type 1 oncoproteins to the transformation of equine fibroblasts.
J Gen Virol, 92(Pt 4), 773-783.
https://doi.org/10.1099/vir.0.028191-0 Publication
Researcher Affiliations
- School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Campus, Bearsden Road, Glasgow G61 1QH, UK.
MeSH Terms
- Animals
- Bovine papillomavirus 1 / pathogenicity
- Cell Proliferation
- Cell Transformation, Neoplastic
- Cells, Cultured
- Equidae
- Fibroblasts / virology
- Gene Knockdown Techniques
- Oncogene Proteins, Viral / genetics
- Oncogene Proteins, Viral / metabolism
Citations
This article has been cited 12 times.- Jindra C, Hainisch EK, Brandt S. Immunotherapy of Equine Sarcoids-From Early Approaches to Innovative Vaccines.. Vaccines (Basel) 2023 Mar 30;11(4).
- 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).
- 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.
- Jindra C, Hainisch EK, Rümmele A, Wolschek M, Muster T, Brandt S. Influenza virus vector iNS1 expressing bovine papillomavirus 1 (BPV1) antigens efficiently induces tumour regression in equine sarcoid patients.. PLoS One 2021;16(11):e0260155.
- de Alcântara BK, Lunardi M, Agnol AMD, Alfieri AF, Alfieri AA. Detection and Quantification of the E6 Oncogene in Bovine Papillomavirus Types 2 and 13 From Urinary Bladder Lesions of Cattle.. Front Vet Sci 2021;8:673189.
- Unger L, Abril C, Gerber V, Jagannathan V, Koch C, Hamza E. Diagnostic potential of three serum microRNAs as biomarkers for equine sarcoid disease in horses and donkeys.. J Vet Intern Med 2021 Jan;35(1):610-619.
- Weber LA, Funtan A, Paschke R, Delarocque J, Kalbitz J, Meißner J, Feige K, Kietzmann M, Cavalleri JV. In vitro assessment of triterpenoids NVX-207 and betulinyl-bis-sulfamate as a topical treatment for equine skin cancer.. PLoS One 2020;15(11):e0241448.
- 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.
- Altamura G, Corteggio A, Nasir L, Yuan ZQ, Roperto F, Borzacchiello G. Analysis of activated platelet-derived growth factor β receptor and Ras-MAP kinase pathway in equine sarcoid fibroblasts.. Biomed Res Int 2013;2013:283985.
- 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.
- Altamura G, Strazzullo M, Corteggio A, Francioso R, Roperto F, D'Esposito M, Borzacchiello G. O(6)-methylguanine-DNA methyltransferase in equine sarcoids: molecular and epigenetic analysis.. BMC Vet Res 2012 Nov 10;8:218.
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