A novel murine model for evaluating bovine papillomavirus prophylactics/therapeutics for equine sarcoid-like tumours

Abstract

Equine sarcoids are highly recurrent bovine papillomavirus (BPV)-induced fibroblastic neoplasms that are the most common skin tumours in horses. In order to facilitate the study of potential equine sarcoid prophylactics or therapeutics, which can be a slow and costly process in equines, a murine model for BPV-1 protein-expressing equine sarcoid-like tumours was developed in mice through stable transfection of BPV-1 E5 and E6 in a murine fibroblast tumour cell line (K-BALB). Like equine sarcoids, these murine tumour cells (BPV-KB) were of fibroblast origin, were tumorigenic and expressed BPV-1 proteins. As an initial investigation of the preclinical potential of this tumour model for equine sarcoids prophylactics, mice were immunized with BPV-1 E5E6 Venezuelan equine encephalitis virus replicon particles, prior to BPV-KB challenge, which resulted in an increased tumour-free period compared with controls, indicating that the BPV-KB murine model may be a valuable preclinical alternative to equine clinical trials.

Recent advances in preclinical model systems for papillomaviruses

“…Another interesting model has arisen from the observation that BPV-1 can cause equine sarcoids in horses (Chambers, Ellsmore et al, 2003). This equine model is amenable to testing immunotherapeutic approaches given that these infections are difficult to treat yet retain BPV-1 viral antigens as foreign targets for T-cell based strategies (Carr, Theon et al, 2001; Chambers, Ellsmore et al, 2003; Bogaert, Woodham et al, 2015). …”

The Induced Expression of BPV E4 Gene in Equine Adult Dermal Fibroblast Cells as a Potential Model of Skin Sarcoid-like Neoplasia

“…We tried to answer the question of which viral genes affect the cell transcriptome, directing changes toward neoplastic transformations, and how. So far, a model of transfected skin cells has been developed in sarcoid research, but it included transfected mouse skin cells [18]. Moreover, this model was not conducted fully in vitro due to the introduction of altered cells into living organisms.…”

“…Previous studies have focused on the analysis of differences in gene expression between sarcoid and normal skin tissues, comparing the transcriptional activities of genes in the cell lines established from these tissues [16,17]. Some studies have aimed to devise in vitro models of murine fibroblast-derived cancerous cell lines generated by transfection with BPV transgenes or to create mouse models of dermal sarcoid-related neoplasia [18]. However, so far there have been no studies that target the development of an ex vivo model of sarcoid-dependent tumorigenesis in equine adult cutaneous fibroblasts cell (ACFC) lines, whose oncogenic transformation has been accomplished by transfection with BPV fusion genes.…”