Genetic variation at IFNL4 influences extrahepatic interferon-stimulated gene expression in chronic HCV patients

Brad R. Rosenberg, Catherine A. Freije, Naoko Imanaka, Spencer T. Chen, Jennifer L. Eitson, Rachel Caron, Skyler A. Uhl, Marija Zeremski, Andrew Talal, Ira M. Jacobson, Charles M. Rice, John W. Schoggins

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Polymorphisms at IFNL4 strongly influence spontaneous resolution and interferon therapeutic response in hepatitis C virus (HCV) infection. In chronic HCV, unfavorable alleles are associated with elevated interferon (IFN)-stimulated gene (ISG) expression in the liver, but extrahepatic effects are less well characterized. We used RNA sequencing (RNA-Seq) to examine whether IFNL4 genetic variation (rs368234815) modulates ISG expression in peripheral blood mononuclear cells (PBMC) during chronic HCV infection. ISG expression was elevated in unstimulated PBMC homozygous for the unfavorable δG IFNL4 variant; expression following IFN-α stimulation was comparable across genotypes. These findings suggest that lambda interferons may have broader systemic effects during HCV infection.

Original languageEnglish (US)
Pages (from-to)650-655
Number of pages6
JournalJournal of Infectious Diseases
Volume217
Issue number4
DOIs
StatePublished - Feb 15 2018

Keywords

  • Hepatitis C
  • IFNL4
  • Interferon
  • Interferon-stimulated genes
  • Peripheral blood mononuclear cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Rosenberg, B. R., Freije, C. A., Imanaka, N., Chen, S. T., Eitson, J. L., Caron, R., Uhl, S. A., Zeremski, M., Talal, A., Jacobson, I. M., Rice, C. M., & Schoggins, J. W. (2018). Genetic variation at IFNL4 influences extrahepatic interferon-stimulated gene expression in chronic HCV patients. Journal of Infectious Diseases, 217(4), 650-655. https://doi.org/10.1093/infdis/jix593