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Mol Cell Biol. 2015 Oct 12;36(1):13-29. doi: 10.1128/MCB.00641-15. Print 2016 Jan 1.

β-Catenin Upregulates the Constitutive and Virus-Induced Transcriptional Capacity of the Interferon Beta Promoter through T-Cell Factor Binding Sites.

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INSERM UMR-S1007, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Institut Pasteur, Unité de Génétique Fonctionnelle de la Souris, Paris, France Centre National de la Recherche Scientifique URA 2578, Paris, France.
Institut Pasteur, Unité de Recherche de Virologie Structurale, Paris, France.
INSERM UMR-S1124, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
INSERM UMR-S1007, Université Paris Descartes, Sorbonne Paris Cité, Paris, France


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.

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