Genetic Variation at IFNL4 Influences Extrahepatic Interferon-Stimulated Gene Expression in Chronic HCV Patients. (20th November 2017)

• Record Type: Journal Article
• Authors: Rosenberg, Brad R; Freije, Catherine A; Imanaka, Naoko; Chen, Spencer T; Eitson, Jennifer L; Caron, Rachel; Uhl, Skyler A; Zeremski, Marija; Talal, Andrew; Jacobson, Ira M; Rice, Charles M; Schoggins, John W
• Is Part Of: Journal of infectious diseases. Volume 217:Number 4(2018)
• Page Start: 650
• Page End: 655
• Publication Date: 2017-11-20
• Subjects: Hepatitis C -- interferon -- interferon-stimulated genes -- IFNL4 -- peripheral blood mononuclear cells; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jix593
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract : In chronic hepatitis C virus (HCV) infection, IFNL4 genetic variation influences hepatic interferon-stimulated gene (ISG) expression. Here, RNA sequencing analysis demonstrated that clinically unfavorable IFNL4 polymorphisms are associated with elevated ISG expression by peripheral blood mononuclear cells in chronic HCV. 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.