2015
The interferon-related developmental regulator 1 is used by human papillomavirus to suppress NFκB activation
Publication
Publication
Nature Communications , Volume 6
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.
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doi.org/10.1038/ncomms7537, hdl.handle.net/1765/86472 | |
Nature Communications | |
Organisation | Department of Pediatrics |
Tummers, B., Goedemans, R., Pelascini, L. P. L., Jordanova, E. S., Van Esch, E. M. G., Meyers, C., … van der Burg, S. (2015). The interferon-related developmental regulator 1 is used by human papillomavirus to suppress NFκB activation. Nature Communications, 6. doi:10.1038/ncomms7537 |