Keratinocyte sensitization to tumour necrosis factor-induced nuclear factor kappa B activation by the E2 regulatory protein of human papillomaviruses.

Manel Boulabiar (1, 2) , Samir Boubaker (1) , Michel Favre (2) , Caroline Demeret (2)

1 Institut Pasteur de Tunis
2 Génétique, Papillomavirus et Cancer Humain

Human Papillomavirus life cycle requires extensive manipulation of cell signaling to provide conditions adequate for viral replication within stratified epithelia. In this regard, we show that the E2 regulatory protein of α, β and μ-HPV genotypes enhances TNF-induced activation of NFκB. This activation is mediated by the N-terminal domain of E2, but does not rely on its transcriptional properties. It is independent of the NFκB regulator Tax1BP1, which nevertheless interacts with all the E2 proteins. E2 specifically activates NFκB pathways induced by TNF, while IL1-induced pathways are not affected. E2 stimulates the activating K63-linked ubiquitination of TRAF5, and interacts with both TRAF5 and TRAF6. Our data suggest that E2 potentiates TNF-induced NFκB signaling mediated by TRAF5 activation through direct binding. Since NFκB controls epithelial differentiation, this activity may be involved in commitment of infected keratinocytes to proliferation arrest and differentiation, both required for implementation of the productive viral cycle.

Domains: Virology

Manel Boulabiar, Samir Boubaker, Michel Favre, Caroline Demeret. Keratinocyte sensitization to tumour necrosis factor-induced nuclear factor kappa B activation by the E2 regulatory protein of human papillomaviruses.. Journal of General Virology, 2011, 92 (10), pp.2422-2427. ⟨10.1099/vir.0.032466-0⟩. ⟨pasteur-00620950⟩