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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 ?G IFNL4 variant; expression following IFN-? stimulation was comparable across genotypes. These findings suggest that lambda interferons may have broader systemic effects during HCV infection.

SUBMITTER: Rosenberg BR 

PROVIDER: S-EPMC5853921 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Genetic Variation at IFNL4 Influences Extrahepatic Interferon-Stimulated Gene Expression in Chronic HCV Patients.

Rosenberg Brad R BR   Freije Catherine A CA   Imanaka Naoko N   Chen Spencer T ST   Eitson Jennifer L JL   Caron Rachel R   Uhl Skyler A SA   Zeremski Marija M   Talal Andrew A   Jacobson Ira M IM   Rice Charles M CM   Schoggins John W JW  

The Journal of infectious diseases 20180101 4


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  ...[more]

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