comparative analysis of the lambda-interferons il-28a and il-29 regarding their transcriptome and their antiviral properties against hepatitis c virus比较分析的lambda-interferons il-28a il-29关于他们的转录组和抗病毒性能对丙型肝炎病毒.pdfVIP

Comparative Analysis of the Lambda-Interferons IL-28A and IL-29 regarding Their Transcriptome and Their Antiviral Properties against Hepatitis C Virus 1 1 1 2 ¨ 1 Julia Diegelmann , Florian Beigel , Kathrin Zitzmann , Artur Kaul , Burkhard Goke , Christoph J. Auernhammer1, Ralf Bartenschlager2, Helmut M. Diepolder 1, Stephan Brand 1* 1 Department of Medicine II, University Hospital Munich-Grosshadern, University of Munich, Munich, Germany, 2 Department of Molecular Virology, University of Heidelberg, Heidelberg, Germany Abstract Background: Specific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. Methodology/Principal Findings: Expression studies were performed by microarray analysis, quantitative PCR (qPCR), reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-l receptor subunits IL-10R2 and IFN-lR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes), many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272