Reduced IFNλ4 activity is associated with improved HCV clearance and reduced expression of interferon-stimulated genes
| Autor: | Vincent Aubert, Beat Müllhaupt, Emilie Collinet, Zoltán Kutalik, Pierre-Yves Bochud, Francesco Negro, Stéphanie Bibert, Darius Moradpour, David Semela, Rune Hartmann, Laurent Kaiser, Ilona Krol, Andreas Cerny, Rosanna Santoro, Raffaele Malinverni, Ewa Terczyńska-Dyla, Nasser Semmo, Markus H. Heim, Alessandra Mangia, Sanne Jørgensen, Francois H.T. Duong |
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| Přispěvatelé: | Swiss Hepatitis C Cohort Study Group, Rubbia-Brandt, L., Martinetti, G., Gorgievski, M., Dufour, JF., Hirsch, H., Helbling B. |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Oxidoreductases Acting on CH-CH Group Donors
Cirrhosis Hepatitis C virus General Physics and Astronomy Locus (genetics) Hepacivirus Biology ddc:616.07 medicine.disease_cause Chronic liver disease General Biochemistry Genetics and Molecular Biology Cell Line Interferon Acetyltransferases medicine Humans Gene Ubiquitins ddc:616 Multidisciplinary Interleukins Membrane Proteins Proteins General Chemistry medicine.disease Hepatitis C 3. Good health Hepatocellular carcinoma Immunology Cytokines Clearance rate medicine.drug Transcription Factors |
| Zdroj: | Nature Communications, vol. 5, pp. 5699 Nature communications Nature Communications, Vol. 5 (2014) P. 5699 Terczynska-Dyla, E, Bibert, S, Duong, F H T, 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, Swiss Hepatitis C Cohort Study Group, Heim, M H, Bochud, P-Y & Hartmann, R 2014, ' Reduced IFNλ4 activity is associated with improved HCV clearance and reduced expression of interferon-stimulated genes ', Nature Communications, vol. 5, 5699 . https://doi.org/10.1038/ncomms6699 |
| ISSN: | 2041-1723 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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