title: The bovine papillomavirus oncoprotein E5 retains MHC class I molecules in the Golgi apparatus and prevents their transport to the cell surface.
abstract: During papillomavirus infection, the E5 protein localizes in the cell Golgi apparatus and other endomembrane compartments. Cells transformed by E5 do not express major histocompatibility class I complex (MHC I) on the cell surface, while cells transformed by the other transforming proteins E6 and E7 do. In addition, the total amount of both MHC I protein and mRNA is reduced in E5-transformed cells. Here we show that expression of bovine papillomavirus E5 causes the retention of MHC I in the Golgi apparatus, thus preventing its transport to the cell surface. We ascribe this effect to a failure of acidification of the Golgi apparatus, as similar effects are observed in control cells treated with the ionophore monensin. Treatment of E5-transformed cells with either beta- or gamma-interferon increases the synthesis of MHC I, showing that inhibition of MHC I expression by E5 is not irreversible. However, even after interferon treatment, MHC I, although increased in quantity, is not transported to the cell surface. E5 therefore affects MHC I at several levels, but prevention of MHC I transport to the cell surface appears to be the dominant effect. Lack of surface MHC I would have profound consequences for presentation of viral peptides to the immune system.
authors.affiliation: Institute of Comparative Medicine, Glasgow University Veterinary School, Garscube Estate, Glasgow G61 1QH, UK.
authors.forename: Barbara
authors.initials: B
authors.lastname: Marchetti
authors.forename: G Hossein
authors.initials: GH
authors.lastname: Ashrafi
authors.forename: Emmanouella
authors.initials: E
authors.lastname: Tsirimonaki
authors.forename: Philippa M
authors.initials: PM
authors.lastname: O'Brien
authors.forename: M Saveria
authors.initials: MS
authors.lastname: Campo
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D052688:Bovine papillomavirus 1 / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D002472:Cell Transformation, Viral; D005786:Gene Expression Regulation / Q000187:drug effects; D005805:Genes, MHC Class I; D017930:Genes, Reporter; D006056:Golgi Apparatus / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008985:Monensin / Q000494:pharmacology; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000502:physiology
chemical_list: D000998:Antiviral Agents; C086266:E7 protein, Bovine papillomavirus type 4; D015395:Histocompatibility Antigens Class I; D007476:Ionophores; D008164:Luminescent Proteins; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; C054304:oncogene protein E5, Bovine papillomavirus type 1; C075621:oncogene protein E7, Bovine papillomavirus type 1; C059269:protein E6, Bovine papillomavirus; D049452:Green Fluorescent Proteins; D016899:Interferon-beta; D007371:Interferon-gamma; D008985:Monensin