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High-risk human papillomavirus E7 expression reduces cell-surface MHC class I molecules and increases susceptibility to natural killer cells

Oncogene volume 27, pages 1794–1799 (2008)Cite this article

Abstract

High-risk human papillomavirus (HPV) is a major causative agent of cervical cancer and the E6 and E7 genes encode the major HPV oncoproteins. The E7 protein from high-risk HPV types alters cell cycle progression and represses genes encoding components of the antigen-presentation pathway, suggesting a role for E7 in tumour immune evasion. We show that knockdown of E7 expression in HPV16- and HPV18-transformed cervical carcinoma cells by RNA interference increased expression of major histocompatibility complex (MHC) class I at the cell surface and reduced susceptibility of these cells to natural killer (NK) cells. Tetracycline-regulated induction of HPV16 E7 resulted in reduced expression of cell surface MHC class I molecules and increased NK cell killing. Our results suggest that, for HPV-associated malignancies, reduced MHC class I expression is the result of an active immune evasion strategy that has evolved to assist viral replication.

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Acknowledgements

We thank Dr M Jiang and Professor AJ Milner for advice on siRNA transfection, Dr J Pines for WT8 cells and A Trejdosiewicz and J Jarvis for technical assistance. This research was supported by Yorkshire Cancer Research, the Medical Research Council (UK) and the Danish Research Council for Nature and the Universe.

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Authors and Affiliations

  1. Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK

    G Bottley, O G Watherston, Y-L Hiew & G E Blair

  2. Institute of Cellular and Molecular Medicine, Panum Institute, University of Copenhagen, Copenhagen N, Denmark

    B Norrild

  3. Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, UK

    G P Cook

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  1. G Bottley
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  2. O G Watherston
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  6. G E Blair
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Correspondence to G E Blair.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Bottley, G., Watherston, O., Hiew, YL. et al. High-risk human papillomavirus E7 expression reduces cell-surface MHC class I molecules and increases susceptibility to natural killer cells. Oncogene 27, 1794–1799 (2008). https://doi.org/10.1038/sj.onc.1210798

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