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The bovine papillomavirus oncoprotein E5 retains MHC class I molecules in the Golgi apparatus and prevents their transport to the cell surface

Oncogene volume 21, pages 7808–7816 (2002)Cite this article

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 β- or γ-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.

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References

  • Agrawal S, Kishore MC . 2000 J. Hematother. Stem Cell Res. 9: 795–812

  • Anderson RA, Scobie L, O'Neil BW, Grindlay GJ, Campo MS . 1997 Vet. J. 154: 69–78

  • Anderson RG, Pathak RK . 1985 Cell 40: 635–643

  • Ashby ADM, Meagher L, Campo MS, Finbow ME . 2001 J. Gen. Virol. 82: 2353–2362

  • Ashrafi GH . 1998 Mutational analysis of the transforming protein E8 (E5) of bovine papillomavirus Type 4 PhD Thesis. Glasgow University, UK

  • Ashrafi GH, Pitts JD, Faccini A, McLean P, O'Brien V, Finbow ME, Campo MS . 2000 J. Gen. Virol. 81: 689–694

  • Ashrafi GH, Tsirimonaki E, Marchetti B, O'Brien PM, Sibbet GJ, Andrew L, Campo MS . 2002 Oncogene 21: 248–259

  • Barr FA, Nakamura N, Warren G . 1998 EMBO J. 17: 3258–3268

  • Bachert C, Lee TH, Linstedt AD . 2001 Mol. Biol. Cell 12: 3152–3160

  • Bensaid A, Kaushal A, Machugh ND, Shapiro SZ, Teale AJ . 1989 Anim. Genet. 20: 241–255

  • Boss WF, Morre' DJ, Mollenhauer HH . 1984 Eur. J. Cell Biol. 34: 1–8

  • Briggs MW, Adam JL, McCance DJ . 2001 Virology 280: 169–175

  • Burkhardt A, Willingham M, Gay C, Jeang KT, Schlegel R . 1989 Virology 170: 334–339

  • Burnett S, Jareborg N, DiMaio D . 1992 Proc. Natl. Acad. Sci. USA 89: 5665–5669

  • Chang JL, Tsao YP, Liu DW, Huang SJ, Lee WH, Chen SL . 2001 J. Biomed. Sci. 8: 206–213

  • Chikuma T, Inomata Y, Tsuchida K, Hojo H, Kato T . 2002 Neurosci. Lett. 326: 89–92

  • Conrad M, Bubb VJ, Schlegel R . 1993 J. Virol. 67: 6170–6178

  • DiMaio D, Mattoon D . 2001 Oncogene 20: 7866–7873

  • Faccini AM, Cairney M, Ashrafi GH, Finbow ME, Campo MS, Pitts JD . 1996 J. Virol. 70: 9041–9045

  • Finbow ME, Harrison M, Jones P . 1995 Bioessays 17: 247–255

  • Franchini G, Mulloy JC, Koralnik IJ, Lo Monico A, Sparkowski JJ, Andresson T, Goldstein DJ, Schlegel R . 1993 J. Virol. 67: 7701–7704

  • Frazer JH, Tindle RW . 1996 Papillomavirus Reviews Lacey C (ed) Leeds, UK: Leeds University Press pp. 151–164

    Google Scholar 

  • Goldstein DJ, Finbow ME, Andresson T, McLean P, Smith K, Bubb V, Schlegel R . 1991 Nature 352: 347–349

  • Graham SP, Jones GE, MacLean M, Livingstone M, Entrican G . 1995 J. Comp. Pathol. 112: 185–195

  • Halaban R, Patton RS, Cheng E, Svedine S, Trombetta ES, Wahl ML, Ariyan S, Hebert DN . 2002 J. Biol. Chem. 277: 14821–14828

  • Ham J, Dostatni N, Gauthier JM, Yaniv M . 1991 Trends Biochem. Sci. 16: 440–444

  • Jackson ME, Pennie WD, McCaffery RE, Smith KT, Grindlay GJ, Campo MS . 1991 Mol. Carcinog. 4: 382–387

  • Johnson JM, Nicot C, Fullen J, Ciminale V, Casareto L, Mulloy JC, Jacobson S, Franchini G . 2001 J. Virol. 75: 6086–6094

  • Mantovani F, Banks L . 2001 Oncogene 20: 7874–7887

  • Morgan IM, Campo MS . 2000 Papillomavirus Report 11: 127–132

  • Munger K, Basile JR, Duensing S, Eichten A, Gonzalez SL, Grace M, Zacny VL . 2001 Oncogene 20: 7888–7898

  • O'Brien PM, Campo MS . 2002 Virus Res. Virus escape from immunosurveillance Campo MS (ed) Shannon, Ireland: Elsevier Science

    Google Scholar 

  • O'Brien V, Ashrafi GH, Grindlay GJ, Anderson R, Campo MS . 1999 Virology. 255: 385–394

  • Oelze I, Kartenbeck J, Crusius K, Alonso A . 1995 J. Virol. 69: 4489–4494

  • Pennie WD, Grindlay GJ, Cairney M, Campo MS . 1993 Virology 193: 614–620

  • Raposo G, Martien van Santen H, Leijendekker R, Geuze HJ, Ploegh HL . 1995 J. Cell Biol. 131: 1403–1419

  • Schapiro F, Sparkowski J, Adduci A, Suprynowicz F, Schlegel R, Grinstein S . 2000 J. Cell Biol. 148: 305–315

  • Schoonderwoert VT, Jansen EJ, Martens GJ . 2002 Eur. J. Biochem. 269: 1844–1853

  • Skinner MA, Wildeman AG . 2001 J. Biol. Chem. 276: 48451–48457

  • Straight SW, Herman B, McCance DJ . 1995 J. Virol. 69: 3185–3192

  • Surti T, Klein O, Aschheim K, DiMaio D, Smith SO . 1998 Proteins 33: 601–612

  • Tartakoff AM . 1983 Cell 32: 1026–1028

  • Thomsen P, van Deurs B, Norrild B, Kayser L . 2000 Oncogene 19: 6023–6032

  • Tindle RW . 2002 Nat. Rev. Cancer 2: 59–65

  • Toye PG, MacHugh ND, Bensaid AM, Alberti S, Teale AJ, Morrison WI . 1990 Immunology 70: 20–26

  • Yewdell JW, Bennink JR . 1999 Ann. Rev. Cell Dev. Biol. 15: 579–606

  • Zhang GF, Driouich A, Staehelin LA . 1993 J. Cell Sci. 104: 819–831

  • Zhang GF, Driouich A, Staehelin LA . 1996 Eur. J. Cell Biol. 71: 332–340

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Acknowledgements

We thank Dr Robina Ullah for her measurements of MHC I heavy chain and E5 mRNA in IFN-treated cells. We are indebted to Drs Shirley Ellis, Gary Entrican, Liz Glass, Martin Lowe, Stuart Ford and Simon Powis for their kind gifts of reagents. We thank Dr Simon Powis for his critical reading of the manuscript. This work was supported by the Medical Research Council, the Association for International Cancer Research and Cancer Research UK (formerly Cancer Research Campaign). MS Campo is a Fellow of Cancer Research UK.

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  1. Institute of Comparative Medicine, Glasgow University Veterinary School, Garscube Estate, Glasgow, G61 1QH, UK

    Barbara Marchetti, G Hossein Ashrafi, Emmanouella Tsirimonaki, Philippa M O'Brien & M Saveria Campo

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  1. Barbara Marchetti
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  2. G Hossein Ashrafi
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  3. Emmanouella Tsirimonaki
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  4. Philippa M O'Brien
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  5. M Saveria Campo
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Correspondence to M Saveria Campo.

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Marchetti, B., Ashrafi, G., Tsirimonaki, E. et al. The bovine papillomavirus oncoprotein E5 retains MHC class I molecules in the Golgi apparatus and prevents their transport to the cell surface. Oncogene 21, 7808–7816 (2002). https://doi.org/10.1038/sj.onc.1205885

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