Terczyńska-Dyla, Ewa; Bibert, Stephanie; Duong, Francois H. T.; Krol, Ilona; Jørgensen, Sanne; Collinet, Emilie; Kutalik, Zoltán; Aubert, Vincent; Cerny, Andreas; Kaiser, Laurent; Malinverni, Raffaele; Mangia, Alessandra; Moradpour, Darius; Müllhaupt, Beat; Negro, Francesco; Santoro, Rosanna; Semela, David; Semmo, Nasser; Rubbia-Brandt, Laura; Martinetti, Gladys; ... (2014). Reduced IFNλ4 activity is associated with improved HCV clearance and reduced expression of interferon-stimulated genes. Nature communications, 5, p. 5699. Nature Publishing Group 10.1038/ncomms6699
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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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie |
UniBE Contributor: |
Cerny, Andreas, Semmo, Nasser, Dufour, Jean-François |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
2041-1723 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Lilian Karin Smith-Wirth |
Date Deposited: |
20 Mar 2015 13:41 |
Last Modified: |
05 Dec 2022 14:44 |
Publisher DOI: |
10.1038/ncomms6699 |
PubMed ID: |
25534433 |
BORIS DOI: |
10.7892/boris.65352 |
URI: |
https://boris.unibe.ch/id/eprint/65352 |
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