Genome-wide RNAi Screen Reveals a New Role of a WNT/CTNNB1 Signaling Pathway as Negative Regulator of Virus-induced Innate Immune Responses | Zendy

Martin Baril | Zendy; Salwa Es-Saad | Zendy; Laurent ChatelChaix | Zendy; Karin Fink | Zendy; Tram N. Q. Pham | Zendy; Valérie–Ann Raymond | Zendy; Karine Audette | Zendy; Anne-Sophie Guenier | Zendy; Jean Duchaine | Zendy; Marc J. Servant | Zendy; Marc Bilodeau | Zendy; Éric A. Cohen | Zendy; Nathalie Grandvaux | Zendy; Daniel Lamarre | Zendy

Open Access

Genome-wide RNAi Screen Reveals a New Role of a WNT/CTNNB1 Signaling Pathway as Negative Regulator of Virus-induced Innate Immune Responses

Author(s) -

Martin Baril,

Salwa Es-Saad,

Laurent ChatelChaix,

Karin Fink,

Tram N. Q. Pham,

Valérie–Ann Raymond,

Karine Audette,

Anne-Sophie Guenier,

Jean Duchaine,

Marc J. Servant,

Marc Bilodeau,

Éric A. Cohen,

Nathalie Grandvaux,

Daniel Lamarre

Publication year - 2013

Publication title -

plos pathogens

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.719

H-Index - 206

eISSN - 1553-7374

pISSN - 1553-7366

DOI - 10.1371/journal.ppat.1003416

Subject(s) - innate immune system , biology , wnt signaling pathway , mda5 , rig i , rna interference , gene knockdown , sendai virus , microbiology and biotechnology , signal transduction , irf3 , interferon , effector , gene silencing , intrinsic immunity , immune system , gene , virus , virology , genetics , rna

To identify new regulators of antiviral innate immunity, we completed the first genome-wide gene silencing screen assessing the transcriptional response at the interferon-β ( IFNB1 ) promoter following Sendai virus (SeV) infection. We now report a novel link between WNT signaling pathway and the modulation of retinoic acid-inducible gene I (RIG-I)-like receptor (RLR)-dependent innate immune responses. Here we show that secretion of WNT2B and WNT9B and stabilization of β-catenin (CTNNB1) upon virus infection negatively regulate expression of representative inducible genes IFNB1 , IFIT1 and TNF in a CTNNB1-dependent effector mechanism. The antiviral response is drastically reduced by glycogen synthase kinase 3 (GSK3) inhibitors but restored in CTNNB1 knockdown cells. The findings confirm a novel regulation of antiviral innate immunity by a canonical-like WNT/CTNNB1 signaling pathway. The study identifies novel avenues for broad-spectrum antiviral targets and preventing immune-mediated diseases upon viral infection.

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