Genome-wide RNAi screen reveals a new role of a WNT/CTNNB1 signaling pathway as negative regulator of virus-induced innate immune responses.
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 modul...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC3681753?pdf=render |
| _version_ | 1818163342130282496 |
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| author | Martin Baril Salwa Es-Saad Laurent Chatel-Chaix Karin Fink Tram Pham Valérie-Ann Raymond Karine Audette Anne-Sophie Guenier Jean Duchaine Marc Servant Marc Bilodeau Eric Cohen Nathalie Grandvaux Daniel Lamarre |
| author_facet | Martin Baril Salwa Es-Saad Laurent Chatel-Chaix Karin Fink Tram Pham Valérie-Ann Raymond Karine Audette Anne-Sophie Guenier Jean Duchaine Marc Servant Marc Bilodeau Eric Cohen Nathalie Grandvaux Daniel Lamarre |
| author_sort | Martin Baril |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T16:48:02Z |
| format | Article |
| id | doaj.art-c8b8b337593f48b0be8e972cb125c37c |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-11T16:48:02Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-c8b8b337593f48b0be8e972cb125c37c2022-12-22T00:58:11ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-01-0196e100341610.1371/journal.ppat.1003416Genome-wide RNAi screen reveals a new role of a WNT/CTNNB1 signaling pathway as negative regulator of virus-induced innate immune responses.Martin BarilSalwa Es-SaadLaurent Chatel-ChaixKarin FinkTram PhamValérie-Ann RaymondKarine AudetteAnne-Sophie GuenierJean DuchaineMarc ServantMarc BilodeauEric CohenNathalie GrandvauxDaniel LamarreTo 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.http://europepmc.org/articles/PMC3681753?pdf=render |
| spellingShingle | Martin Baril Salwa Es-Saad Laurent Chatel-Chaix Karin Fink Tram Pham Valérie-Ann Raymond Karine Audette Anne-Sophie Guenier Jean Duchaine Marc Servant Marc Bilodeau Eric Cohen Nathalie Grandvaux Daniel Lamarre Genome-wide RNAi screen reveals a new role of a WNT/CTNNB1 signaling pathway as negative regulator of virus-induced innate immune responses. PLoS Pathogens |
| title | Genome-wide RNAi screen reveals a new role of a WNT/CTNNB1 signaling pathway as negative regulator of virus-induced innate immune responses. |
| title_full | Genome-wide RNAi screen reveals a new role of a WNT/CTNNB1 signaling pathway as negative regulator of virus-induced innate immune responses. |
| title_fullStr | Genome-wide RNAi screen reveals a new role of a WNT/CTNNB1 signaling pathway as negative regulator of virus-induced innate immune responses. |
| title_full_unstemmed | Genome-wide RNAi screen reveals a new role of a WNT/CTNNB1 signaling pathway as negative regulator of virus-induced innate immune responses. |
| title_short | Genome-wide RNAi screen reveals a new role of a WNT/CTNNB1 signaling pathway as negative regulator of virus-induced innate immune responses. |
| title_sort | genome wide rnai screen reveals a new role of a wnt ctnnb1 signaling pathway as negative regulator of virus induced innate immune responses |
| url | http://europepmc.org/articles/PMC3681753?pdf=render |
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