Richards, KH, Wasson, CW, Watherston, O et al. (4 more authors) (2015) The human papillomavirus (HPV) E7 protein antagonises an Imiquimod-induced inflammatory pathway in primary human keratinocytes. Scientific Reports, 5. 12922. ISSN 2045-2322
Abstract
High-risk human papillomaviruses (HPV) are the etiological pathogen of cervical and a number of ano-genital cancers. How HPVs overcome the significant barriers of the skin immune system has been the topic of intensive research. The E6 and E7 oncoproteins have emerged as key players in the deregulation of host innate immune pathways that are required for the recruitment of effector cells of the immune response. Here we demonstrate that E7, and to a lesser extend E6, strongly reduce NFB activation in response to the inflammatory mediator imiquimod. Moreover, we establish that undifferentiated keratinocytes do not express the putative receptor for imiquimod, TLR7, and as such are stimulated by imiquimod through a novel pathway. Inhibition of imiquimod induced cytokine production required residues in the CR1 and CR3 regions of E7 and resulted in reduced nuclear translocation and acetylation of the p65 sub-unit of NFB. The results provide further evidence for a TLR7-independent role of imiquimod in the epithelial immune response and reinforce the ability of the HPV oncoproteins to disrupt the innate immune response, which may have important consequences for establishment of a chronic infection.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015 The author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
Keywords: | human papilloma virus; pattern recognition receptors |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Clinical Musculoskeletal Medicine (LIRMM) (Leeds) |
Funding Information: | Funder Grant number Yorkshire Cancer Research L339 Yorkshire Cancer Research PP015 Yorkshire Cancer Research LPP041 Cancer Research UK C43832/A14246 MRC MR/K012665/1 |
Depositing User: | Symplectic Publications |
Date Deposited: | 15 Jul 2015 10:55 |
Last Modified: | 11 Mar 2016 09:36 |
Published Version: | http://dx.doi.org/10.1038/srep12922 |
Status: | Published |
Publisher: | Nature Publishing Group |
Identification Number: | 10.1038/srep12922 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:87983 |