Reduced IFNλ4 activity is associated with improved HCV clearance and reduced expression of interferon-stimulated genes

Détails

Ressource 1Télécharger: BIB_84F2B7901E6D.P001.pdf (413.97 [Ko])
Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_84F2B7901E6D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Reduced IFNλ4 activity is associated with improved HCV clearance and reduced expression of interferon-stimulated genes
Périodique
Nature Communications
Auteur(s)
Terczyńska-Dyla E., Bibert S., Duong F.H., Krol I., Jørgensen S., Collinet E., Kutalik Z., Aubert V., Cerny A., Kaiser L., Malinverni R., Mangia A., Moradpour D., Müllhaupt B., Negro F., Santoro R., Semela D., Semmo N., Heim M.H., Heim M.H., Bochud P.Y., Hartmann R.
Collaborateur(s)
Swiss Hepatitis C Cohort Study Group, Swiss Hepatitis C Cohort Study Group
Contributeur(s)
Rubbia-Brandt L., Martinetti G., Gorgievski M., Dufour JF., Hirsch H., Helbling B.<AffiliationInfo> <Affiliation>1] [2].</Affiliation></AffiliationInfo> , Regenass S., Dollenmaier G., Cathomas G.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
5
Pages
5699
Langue
anglais
Notes
Publication types: Journal Article Publication Status: epublish
Résumé
Hepatitis C virus (HCV) infections are the major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma worldwide. Both spontaneous and treatment-induced clearance of HCV depend on genetic variation within the interferon-lambda locus, but until now no clear causal relationship has been established. Here we demonstrate that an amino-acid substitution in the IFNλ4 protein changing a proline at position 70 to a serine (P70S) substantially alters its antiviral activity. Patients harbouring the impaired IFNλ4-S70 variant display lower interferon-stimulated gene (ISG) expression levels, better treatment response rates and better spontaneous clearance rates, compared with patients coding for the fully active IFNλ4-P70 variant. Altogether, these data provide evidence supporting a role for the active IFNλ4 protein as the driver of high hepatic ISG expression as well as the cause of poor HCV clearance.
Pubmed
Web of science
Création de la notice
10/01/2015 14:35
Dernière modification de la notice
03/03/2018 18:56
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