School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Campus, Bearsden Road, Glasgow G61 1QH, UK.
J Gen Virol. 2011 Apr;92(Pt 4):773-83. doi: 10.1099/vir.0.028191-0. Epub 2010 Dec 22.
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.
马的肉瘤是世界范围内马属动物最常见的皮肤肿瘤，其特征为局部侵袭，罕见自发消退，且手术后极易复发。牛乳头瘤病毒 1 型（BPV-1）和较少见的 BPV-2 现已被广泛认为是该病的致病因子。从肉瘤中分离出的成纤维细胞具有很强的侵袭性。侵袭与病毒基因表达水平升高和基质金属蛋白酶上调有关。然而，BPV-1 蛋白在多大程度上参与了马属动物细胞的转化仍不清楚。为了解决这个问题，我们在正常马成纤维细胞（EqPalF 细胞）和永生化但不完全转化的肉瘤衍生的 EqS02a 细胞系中过表达了单个病毒基因 E5、E6 和 E7。评估了这些细胞系的增殖和侵袭能力。结果发现 E5 和 E6 负责增强 EqS02a 细胞的增殖和诱导侵袭增加，而 E7 似乎增强了细胞的锚定独立性。通过小干扰 RNA 敲低 BPV-1 癌基因表达，逆转了肉瘤成纤维细胞的转化表型。综上所述，这些观察结果强烈表明 BPV-1 蛋白在马属动物成纤维细胞的转化中起着不可或缺的作用。这些数据还表明，BPV-1 蛋白可能是马属动物肉瘤治疗的潜在药物靶点。
