Transcriptional changes induced by Bovine Papillomavirus type 1 in equine fibroblasts

Institute of Comparative Medicine, University of Glasgow Faculty of Veterinary Medicine, Bearsden Road, Glasgow G61 1QH, UK

^* To whom correspondence should be addressed. Email: l.nasir{at}vet.gla.ac.uk.

	Abstract

Bovine Papillomavirus type 1 (BPV-1) and less commonly BPV-2 are associated with the pathogenesis of common equine skin tumours termed sarcoids. In an attempt to understand the mechanisms by which BPV-1 induces sarcoids, we used gene expression profiling as a screening tool to identify candidates genes implicated in disease pathogenesis. Gene expression profiles of equine fibroblasts transformed by BPV-1 either experimentally or from explanted tumours were compared with control equine fibroblasts to identify genes associated with expression of BPV-1. Analysis of the microarray data identified 81 probe sets that were significantly (p < 0.01) differentially expressed between the BPV-1 transformed and control cell lines. Expression of several deregulated genes including MMP-1, CXCL5, FRA-1, NKG7, MHC class I and TLR4 was confirmed in other BPV-1 transformed cell lines. Furthermore, expression of these genes was examined in a panel of 10 sarcoids. Increased expression of MMP-1, CXCL5, FRA-1 and NKG7 was detected in a subset of tumours and TLR4 and MHC class I showed a robust down-regulation in all tumours. De-regulated expression was confirmed at the protein level for MMP-1 and MHC I. The present work identifies genes modulated by BPV-1 transformation and will help identify the molecular mechanisms involved in disease pathogenesis.