The interferon-related developmental regulator 1 is used by human papillomavirus to suppress NFκB activation

Bart Tummers, Renske Goedemans, Laetitia P.L. Pelascini, Ekaterina S. Jordanova, Edith M.G. Van Esch, Craig Meyers, Cornelis J.M. Melief, Judith M. Boer, Sjoerd H. Van Der Burg

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

High-risk human papillomaviruses (hrHPVs) infect keratinocytes and successfully evade host immunity despite the fact that keratinocytes are well equipped to respond to innate and adaptive immune signals. Using non-infected and freshly established or persistent hrHPV-infected keratinocytes we show that hrHPV impairs the acetylation of NFκB/RelA K310 in keratinocytes. As a consequence, keratinocytes display a decreased pro-inflammatory cytokine production and immune cell attraction in response to stimuli of the innate or adaptive immune pathways. HPV accomplishes this by augmenting the expression of interferon-related developmental regulator 1 (IFRD1) in an EGFR-dependent manner. Restoration of NFκB/RelA acetylation by IFRD1 shRNA, cetuximab treatment or the HDAC1/3 inhibitor entinostat increases basal and induced cytokine expression. Similar observations are made in IFRD1-overexpressing HPV-induced cancer cells. Thus, our study reveals an EGFR-IFRD1-mediated viral immune evasion mechanism, which can also be exploited by cancer cells.

Original languageEnglish (US)
Article number6537
JournalNature communications
Volume6
DOIs
StatePublished - 2015

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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