Published in

Nature Research, Nature Communications, 1(6), 2015

DOI: 10.1038/ncomms8280

Nature Research, Nature Communications, 1(5), 2014

DOI: 10.1038/ncomms6699

Links

Tools

Export citation

Search in Google Scholar

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

Journal article published in 2014 by Ewa Terczyńska-Dyla, Stephanie Bibert, Francois H. T. Duong, Ilona Krol, Sanne Jørgensen, Emilie Collinet, Zoltán Kutalik, Vincent Aubert, Andreas Cerny, Laurent Kaiser, Raffaele Malinverni, Alessandra Mangia, Darius Moradpour, Beat Müllhaupt, Francesco Negro and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

Full text: Download

Green circle
Preprint: archiving allowed
Upload
Red circle
Postprint: archiving forbidden
Green circle
Published version: archiving allowed
Upload
Policy details
Data provided by SHERPA/RoMEO

Abstract

Other ; 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.