Unknown

Dataset Information

0

Differential regulation of human papillomavirus type 8 by interferon regulatory factors 3 and 7.


ABSTRACT: The genus ? human papillomavirus (HPV) type 8 is associated with nonmelanoma skin cancer in patients with epidermodysplasia verruciformis, and evidence for its protumorigenic potential in the general population increases. To date, strategies to suppress genus ? HPV infections are limited. Interferon regulatory factors IRF-3 and IRF-7 play key roles in the activation of the innate immune response to viral infections. In this study, we show for the first time that both IRF-3 and IRF-7 regulate transcription of a papillomavirus, but with opposing effects. IRF-7, expressed in the suprabasal layers of human epidermis, increased HPV8 late promoter activity via direct binding to viral DNA. UV-B light-induced activation of the HPV8 promoter involved IRF-7 as a downstream effector. In contrast, IRF-3, expressed in all layers of human epidermis, induced strong HPV8 suppression in primary keratinocytes. IRF-3-mediated suppression prevailed over IRF-7-induced HPV8 transcription. Unlike the E6 oncoprotein of the mucosal high-risk HPV16, the HPV8 E6 protein did not bind to IRF-3 and only weakly antagonized its activity. Strong antiviral activity was also observed, when keratinocytes were treated with potent IRF-3 activators, poly(I:C) or RNA bearing 5' phosphates. In conclusion, we show that IRF-3 activation induces a state of cell-autonomous immunity against HPV in primary human keratinocytes. Our study suggests that local application of IRF-3-activating compounds might constitute an attractive novel therapeutic strategy against HPV8-associated diseases, particularly in epidermodysplasia verruciformis patients.

SUBMITTER: Oldak M 

PROVIDER: S-EPMC3014176 | BioStudies | 2011-01-01

REPOSITORIES: biostudies

Similar Datasets

2018-01-01 | S-EPMC5845987 | BioStudies
2017-01-01 | S-EPMC5287491 | BioStudies
2017-01-01 | S-EPMC5481020 | BioStudies
2012-01-01 | S-EPMC3406103 | BioStudies
1000-01-01 | S-EPMC5613749 | BioStudies
2019-01-01 | S-EPMC6468676 | BioStudies
2017-01-01 | S-EPMC5609557 | BioStudies
2014-01-01 | S-EPMC4135955 | BioStudies
2019-01-01 | S-EPMC7317279 | BioStudies
2004-01-01 | S-EPMC516394 | BioStudies