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  • Original Paper
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Down-regulation of MHC class I by bovine papillomavirus E5 oncoproteins

Oncogene volume 21, pages 248–259 (2002)Cite this article

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.

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Acknowledgements

We wish to thank the following colleagues for their generous gifts of materials: Dr Liz Glass for mAb IL-A19, Dr Shirley Ellis for mAb IL-A88, Dr Jan Naessens for mAb IL-A165, Dr George Russell for the MCH I heavy chain oligonucleotide primers, Drs Francis Barr and Martin Lowe for mAb 4A3, Prof R Schelegel and Dr S-L Chen for NIH3T3 cells transformed by HPV-16 and HPV-6 E5 respectively. Thanks are due to Mr Ross Blackley for his invaluable help with the EM analysis. We wish to thank also all our colleagues for their comments and stimulating discussions. This work was financially supported by The Cancer Research Campaign. We are grateful to The Royal Society for supporting GH Ashrafi through a Developing World Study Visit Scheme and to Universita' degli Studi di Roma ‘La Sapienza’ for supporting B Marchetti with a Study Visit Fellowship. PM O'Brien is supported by The Association for International Cancer Research and MSC by a Life Fellowship of The Cancer Research Campaign.

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  1. Gary J Sibbet

    Present address: The Beatson Institute for Cancer Research, Garscube Estate, Glasgow, G61 1BD, UK

Authors and Affiliations

  1. Department of Veterinary Pathology, Papillomavirus Research Group, Institute of Comparative Medicine, Glasgow University, Garscube Estate, Glasgow, G61 1QH, UK

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

  2. Department of Veterinary Pathology, LRF Virus Centre, Glasgow University, Garscube Estate, Glasgow, G61 1QH, UK

    Linda Andrew

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Correspondence to M Saveria Campo.

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Ashrafi, G., Tsirimonaki, E., Marchetti, B. et al. Down-regulation of MHC class I by bovine papillomavirus E5 oncoproteins. Oncogene 21, 248–259 (2002). https://doi.org/10.1038/sj.onc.1205008

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