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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Epithelial Cells
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Hepatocytes / cytology
  • Hepatocytes / drug effects*
  • Hepatocytes / physiology*
  • Humans
  • Interleukins / genetics*
  • Interleukins / pharmacology
  • Lung / cytology
  • Lung / physiology
  • Oligonucleotide Array Sequence Analysis
  • Organ Specificity
  • Primary Cell Culture
  • Transcriptome / drug effects


  • IFNL4 protein, human
  • Interleukins