title: Down-regulation of MHC class I by bovine papillomavirus E5 oncoproteins.
abstract: The papillomavirus E5 protein is localized in the endoplasmic reticulum (ER) and Golgi apparatus (GA) of the host cell. Transformed bovine fibroblasts expressing bovine papillomavirus (BPV) E5 are highly vacuolated and have a much enlarged, distorted and fragmented GA. Major histocompatibility complex class I (MHC I) is processed and transported to the cell surface through the GA. Given the cellular localization of E5 in the GA and the morphologically abnormal GA, we investigated the expression of MHC I in cells transformed by E5 from BPV-1 and BPV-4. Two cell lines were used: bovine cells that also express E6, E7 and activated ras, and NIH3T3 cells that express only E5. In addition, PalF cells acutely infected with a recombinant retrovirus expressing E5 were also examined. In contrast to non-transformed normal cells, or transformed cells expressing other papillomavirus proteins, cells expressing E5 do not express MHC I on their surface, but retain it intracellularly, independently of the presence of other viral or cellular oncogenes, or of whether the cells are long-term transformants or acutely infected. We conclude that expression of E5 prevents expression of MHC I to the cell surface and causes its retention within the cell. In addition, lower amounts of total MHC I heavy chain and of heavy chain RNA are detected in E5-transformed cells than in control cells. As surface expression of another glycosylated membrane protein, the transferrin receptor, is not affected, it appears that E5 targets MHC I with at least a degree of specificity. In papillomavirus lesions this effect would have important implications for antigen presentation by, and immunosurveillance of, virally infected cells.
authors.affiliation: Papillomavirus Research Group, Institute of Comparative Medicine, Department of Veterinary Pathology, Glasgow University, Garscube Estate, Glasgow G61 1QH, UK.
authors.forename: G Hossein
authors.initials: GH
authors.lastname: Ashrafi
authors.forename: Emmanouella
authors.initials: E
authors.lastname: Tsirimonaki
authors.forename: Barbara
authors.initials: B
authors.lastname: Marchetti
authors.forename: Philippa M
authors.initials: PM
authors.lastname: O'Brien
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Sibbet
authors.forename: Linda
authors.initials: L
authors.lastname: Andrew
authors.forename: M Saveria
authors.initials: MS
authors.lastname: Campo
mesh_terms: D000818:Animals; D052688:Bovine papillomavirus 1 / Q000235:genetics*; D052697:Bovine papillomavirus 4; D002417:Cattle; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000235:genetics*; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D016296:Mutagenesis; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D015395:Histocompatibility Antigens Class I; D009856:Oncogene Proteins, Viral; C054304:oncogene protein E5, Bovine papillomavirus type 1; D011505:Protein-Tyrosine Kinases