A frequent hypofunctional IRAK2 variant is associated with reduced spontaneous hepatitis C virus clearance.
Détails
ID Serval
serval:BIB_2CAFFC38CBEA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A frequent hypofunctional IRAK2 variant is associated with reduced spontaneous hepatitis C virus clearance.
Périodique
Hepatology (baltimore, Md.)
Collaborateur⸱rice⸱s
Swiss Hepatitis C Virus Study Groups
Contributeur⸱rice⸱s
East-German
ISSN
1527-3350 (Electronic)
ISSN-L
0270-9139
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
62
Numéro
5
Pages
1375-1387
Langue
anglais
Résumé
UNLABELLED: Patients carrying very rare loss-of-function mutations in interleukin-1 receptor-associated kinase 4 (IRAK4), a critical signaling mediator in Toll-like receptor signaling, are severely immunodeficient, highlighting the paramount role of IRAK kinases in innate immunity. We discovered a comparatively frequent coding variant of the enigmatic human IRAK2, L392V (rs3844283), which is found homozygously in ∼15% of Caucasians, to be associated with a reduced ability to induce interferon-alpha in primary human plasmacytoid dendritic cells in response to hepatitis C virus (HCV). Cytokine production in response to purified Toll-like receptor agonists was also impaired. Additionally, rs3844283 was epidemiologically associated with a chronic course of HCV infection in two independent HCV cohorts and emerged as an independent predictor of chronic HCV disease. Mechanistically, IRAK2 L392V showed intact binding to, but impaired ubiquitination of, tumor necrosis factor receptor-associated factor 6, a vital step in signal transduction.
CONCLUSION: Our study highlights IRAK2 and its genetic variants as critical factors and potentially novel biomarkers for human antiviral innate immunity. (Hepatology 2015;62:1375-1387).
CONCLUSION: Our study highlights IRAK2 and its genetic variants as critical factors and potentially novel biomarkers for human antiviral innate immunity. (Hepatology 2015;62:1375-1387).
Pubmed
Web of science
Open Access
Oui
Création de la notice
21/08/2015 15:51
Dernière modification de la notice
20/08/2019 14:11