The bovine papillomavirus oncoprotein E5 retains MHC class I molecules in the Golgi apparatus and prevents their transport to the cell surface.
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.
Marchetti
Barbara
B
Institute of Comparative Medicine, Glasgow University Veterinary School, Garscube Estate, Glasgow G61 1QH, UK.
Ashrafi
G Hossein
GH
Tsirimonaki
Emmanouella
E
O'Brien
Philippa M
PM
Campo
M Saveria
MS
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
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