title: β-Catenin Upregulates the Constitutive and Virus-Induced Transcriptional Capacity of the Interferon Beta Promoter through T-Cell Factor Binding Sites.
abstract: Rapid upregulation of interferon beta (IFN-β) expression following virus infection is essential to set up an efficient innate antiviral response. Biological roles related to the antiviral and immune response have also been associated with the constitutive production of IFN-β in naive cells. However, the mechanisms capable of modulating constitutive IFN-β expression in the absence of infection remain largely unknown. In this work, we demonstrate that inhibition of the kinase glycogen synthase kinase 3 (GSK-3) leads to the upregulation of the constitutive level of IFN-β expression in noninfected cells, provided that GSK-3 inhibition is correlated with the binding of β-catenin to the IFN-β promoter. Under these conditions, IFN-β expression occurred through the T-cell factor (TCF) binding sites present on the IFN-β promoter independently of interferon regulatory factor 3 (IRF3). Enhancement of the constitutive level of IFN-β per se was able to confer an efficient antiviral state to naive cells and acted in synergy with virus infection to stimulate virus-induced IFN-β expression. Further emphasizing the role of β-catenin in the innate antiviral response, we show here that highly pathogenic Rift Valley fever virus (RVFV) targets the Wnt/β-catenin pathway and the formation of active TCF/β-catenin complexes at the transcriptional and protein level in RVFV-infected cells and mice.
authors.affiliation: INSERM UMR-S1007, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Vasco
authors.initials: V
authors.lastname: Marcato
authors.affiliation: INSERM UMR-S1007, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Luron
authors.affiliation: INSERM UMR-S1007, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Lucie M
authors.initials: LM
authors.lastname: Laqueuvre
authors.affiliation: Institut Pasteur, Unité de Génétique Fonctionnelle de la Souris, Paris, France Centre National de la Recherche Scientifique URA 2578, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Simon
authors.affiliation: INSERM UMR-S1007, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Zeyni
authors.initials: Z
authors.lastname: Mansuroglu
authors.affiliation: Institut Pasteur, Unité de Recherche de Virologie Structurale, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Flamand
authors.affiliation: Institut Pasteur, Unité de Génétique Fonctionnelle de la Souris, Paris, France Centre National de la Recherche Scientifique URA 2578, Paris, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Panthier
authors.affiliation: INSERM UMR-S1007, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Souès
authors.affiliation: INSERM UMR-S1124, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Charbel
authors.initials: C
authors.lastname: Massaad
authors.affiliation: INSERM UMR-S1007, Université Paris Descartes, Sorbonne Paris Cité, Paris, France eliette.bonnefoy@parisdescartes.fr.
authors.forename: Eliette
authors.initials: E
authors.lastname: Bonnefoy
mesh_terms: D000818:Animals; D001665:Binding Sites; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic; D012296:Rift Valley fever virus; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism*; D051820:TCF Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495267:CTNNB1 protein, mouse; D051820:TCF Transcription Factors; D051176:beta Catenin; D016899:Interferon-beta; D038362:Glycogen Synthase Kinase 3