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Genes Immun. 2015 Sep;16(6):414-21. doi: 10.1038/gene.2015.23. Epub 2015 Jun 11.

Transcriptome analysis reveals a classical interferon signature induced by IFNλ4 in human primary cells.

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Institute for Medical Informatics and Biometry, Technische Universität Dresden, Dresden, Germany.
Institute of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
Institute of Virology and Immunology IVI, Bern, and Vetsuisse Faculty, University of Bern, Länggassstrasse 122, Bern, Switzerland.
Genome Analytics, Helmholtz Centre for Infection Research, Braunschweig, Germany.
German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany.
ReMediES, Department of General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany.


The IFNL4 gene is negatively associated with spontaneous and treatment-induced clearance of hepatitis C virus infection. The activity of IFNλ4 has an important causal role in the pathogenesis, but the molecular details are not fully understood. One possible reason for the detrimental effect of IFNλ4 could be a tissue-specific regulation of an unknown subset of genes. To address both tissue and subtype specificity in the interferon response, we treated primary human hepatocytes and airway epithelial cells with IFNα, IFNλ3 or IFNλ4 and assessed interferon mediated gene regulation using transcriptome sequencing. Our data show a surprisingly similar response to all three subtypes of interferon. We also addressed the tissue specificity of the response, and identified a subset of tissue-specific genes. However, the interferon response is robust in both tissues with the majority of the identified genes being regulated in hepatocytes as well as airway epithelial cells. Thus we provide an in-depth analysis of the liver interferon response seen over an array of interferon subtypes and compare it to the response in the lung epithelium.

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