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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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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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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DOI: https://doi.org/10.1038/sj.onc.1205885
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