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

doi:10.1093/infdis/jix593

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

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15 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 language	English (US)
Pages (from-to)	650-655
Number of pages	6
Journal	Journal of Infectious Diseases
Volume	217
Issue number	4
DOIs	https://doi.org/10.1093/infdis/jix593
State	Published - Feb 15 2018

Keywords

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

ASJC Scopus subject areas

General Medicine

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10.1093/infdis/jix593

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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

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title = "Genetic variation at IFNL4 influences extrahepatic interferon-stimulated gene expression in chronic HCV patients",

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.",

keywords = "Hepatitis C, IFNL4, Interferon, Interferon-stimulated genes, Peripheral blood mononuclear cells",

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

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doi = "10.1093/infdis/jix593",

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T1 - Genetic variation at IFNL4 influences extrahepatic interferon-stimulated gene expression in chronic HCV patients

AU - Rosenberg, Brad R.

AU - Freije, Catherine A.

AU - Imanaka, Naoko

AU - Chen, Spencer T.

AU - Eitson, Jennifer L.

AU - Caron, Rachel

AU - Uhl, Skyler A.

AU - Zeremski, Marija

AU - Talal, Andrew

AU - Jacobson, Ira M.

AU - Rice, Charles M.

AU - Schoggins, John W.

N1 - Publisher Copyright: © The Author(s) 2017.

PY - 2018/2/15

Y1 - 2018/2/15

N2 - 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.

AB - 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.

KW - Hepatitis C

KW - IFNL4

KW - Interferon

KW - Interferon-stimulated genes

KW - Peripheral blood mononuclear cells

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AN - SCOPUS:85044442127

SN - 0022-1899

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SP - 650

EP - 655

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 4

ER -

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

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