Data from: Influence of hepatitis C virus and IL28B genotypes on liver stiffness

负责人：

关键词：

hepatitis C genotypes;Fibrosis progression;single nucleotide polymorphism (SNP);transient elastography;IL28b genotypes;liver cirrhosis

DOI：

doi:10.5061/dryad.0q524

摘要：

Objective: Liver fibrosis has been associated with hepatitis C virus (HCV) genotype and genetic variation near the interleukin 28B (IL28B) gene

Data from: Zinc is a potent and specific inhibitor of IFN-?3 signalling

负责人：

关键词：

il28b;rs12979860;Homo Sapiens;metallothionein;Hepatitis C Virus;zinc;ifnl3

DOI：

doi:10.5061/dryad.n0s75

摘要：

Lambda interferons (IFNL, IFN-?) are pro-inflammatory cytokines important in acute and chronic viral infection. Single-nucleotide polymorphisms rs12979860 and rs8099917 within the IFNL gene locus predict hepatitis C virus (HCV) clearance, as well as inflammation and fibrosis progression in viral and non-viral liver disease. The underlying mechanism, however, is not defined. Here we show that the rs12979860 CC genotype correlates with increased hepatic metallothionein expression through increased systemic zinc levels. Zinc interferes with IFN-?3 binding to IFNL receptor 1 (IFNLR1), resulting in decreased antiviral activity and increased viral replication (HCV, influenza) in vitro. HCV patients with high zinc levels have low hepatocyte antiviral and inflammatory gene expression and high viral loads, confirming the inhibitory role of zinc in vivo. We provide the first evidence that zinc can act as a potent and specific inhibitor of IFN-?3 signalling and highlight its potential as a target of therapeutic intervention for IFN-?3-mediated chronic disease.