期刊
PLOS PATHOGENS
卷 9, 期 6, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1003416
关键词
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资金
- Canadian Institutes for Health Research [CIHR-MOP-115010, CIHR-CI6-103135]
- Genome Quebec (PRIVAC initiative)
- Novartis/Canadian Liver Foundation Hepatology Research Chair
- CIHR Postdoctoral Fellowship
- Canadian Center of Excellence in Commercialization and Research
- Canada Foundation for Innovation (CFI)
- Fonds de Recherche du Quebec en Sante (FRQS)
To identify new regulators of antiviral innate immunity, we completed the first genome-wide gene silencing screen assessing the transcriptional response at the interferon-beta (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 beta-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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