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

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 and 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:

20 Mar 2015 13:41

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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