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Journal of Virology, July 2008, p. 6481-6491, Vol. 82, No. 13
0022-538X/08/$08.00+0     doi:10.1128/JVI.00429-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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, United Kingdom

Received 27 February 2008/ Accepted 16 April 2008

Bovine papillomavirus type 1 (BPV-1) and, less commonly, BPV-2 are associated with the pathogenesis of common equine skin tumors 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 candidate genes implicated in disease pathogenesis. Gene expression profiles of equine fibroblasts transformed by BPV-1 experimentally or from explanted tumors were compared with those of 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, TLR4, and the gene encoding the major histocompatibility complex class I (MHC-I) protein, was confirmed using other BPV-1-transformed cell lines. Furthermore, expression of these genes was examined using a panel of 10 sarcoids. Increased expression of MMP-1, CXCL5, FRA-1, and NKG7 was detected in a subset of tumors, and TLR4 and MHC I showed robust down-regulation in all tumors. Deregulated expression was confirmed at the protein level for MMP-1 and MHC-I. The present report identifies genes modulated by BPV-1 transformation and will help identify the molecular mechanisms involved in disease pathogenesis.

Published ahead of print on 23 April 2008.