Bovine papillomavirus type 1 oncoprotein E5 inhibits equine MHC class I and interacts with equine MHC I heavy chain.
Bovine papillomavirus type 1 is one of the aetiological agents of equine sarcoids. The viral major oncoprotein E5 is expressed in virtually all sarcoids, sarcoid cell lines and in vitro-transformed equine fibroblasts. To ascertain whether E5 behaves in equine cells as it does in bovine cells, we introduced the E5 open reading frame into fetal equine fibroblasts (EqPalF). As observed in primary bovine fibroblasts (BoPalF), E5 by itself could not immortalize EqPalF and an immortalizing gene, such as human telomerase (hTERT/hT), was required for the cells to survive selection. The EqPalF-hT-1E5 cells were morphologically transformed, elongated with many pseudopodia and capable of forming foci. Equine major histocompatibility complex class I (MHC I) was inhibited in these cells at least at two levels: transcription of MHC I heavy chain was inhibited and the MHC I complex was retained in the Golgi apparatus and prevented from reaching the cell surface. We conclude that, as in bovine cells and tumours, E5 is a player in the transformation of equine cells and the induction of sarcoids, and a potential major cause of MHC I downregulation and hence poor immune clearance of tumour cells.
Marchetti
Barbara
B
Institute of Comparative Medicine, University of Glasgow, Glasgow G61 1QH, Scotland, UK.
Gault
Elisabeth A
EA
Institute of Comparative Medicine, University of Glasgow, Glasgow G61 1QH, Scotland, UK.
Cortese
Marc S
MS
Institute of Comparative Medicine, University of Glasgow, Glasgow G61 1QH, Scotland, UK.
Yuan
ZhengQiang
Z
Institute of Comparative Medicine, University of Glasgow, Glasgow G61 1QH, Scotland, UK.
Ellis
Shirley A
SA
Immunology Division, Institute for Animal Health, Compton, UK.
Nasir
Lubna
L
Institute of Comparative Medicine, University of Glasgow, Glasgow G61 1QH, Scotland, UK.
Campo
M Saveria
MS
Institute of Comparative Medicine, University of Glasgow, Glasgow G61 1QH, Scotland, UK.
D000818:Animals; D052688:Bovine papillomavirus 1 / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I; D006056:Golgi Apparatus / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006736:Horses; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D009856:Oncogene Proteins, Viral; C054304:oncogene protein E5, Bovine papillomavirus type 1; D019098:Telomerase