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

Details

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State: Public
Version: author
Serval ID
serval:BIB_84F2B7901E6D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Reduced IFNλ4 activity is associated with improved HCV clearance and reduced expression of interferon-stimulated genes
Journal
Nature Communications
Author(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.
Working group(s)
Swiss Hepatitis C Cohort Study Group, Swiss Hepatitis C Cohort Study Group
Contributor(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
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
5
Pages
5699
Language
english
Notes
Publication types: Journal Article Publication Status: epublish
Abstract
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
Open Access
Yes
Create date
10/01/2015 13:35
Last modification date
20/08/2019 14:44
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