Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus

• Verfasst von: Diegelmann, Julia [VerfasserIn]
• Verfasst von: Beigel, Florian [VerfasserIn]
• Verfasst von: Zitzmann, Kathrin [VerfasserIn]
• Verfasst von: Kaul, Artur [VerfasserIn]
• Verfasst von: Göke, Burkhard [VerfasserIn]
• Verfasst von: Auernhammer, Christoph J. [VerfasserIn]
• Verfasst von: Bartenschlager, Ralf [VerfasserIn]
• Verfasst von: Diepolder, Helmut M. [VerfasserIn]
• Verfasst von: Brand, Stephan [VerfasserIn]
• Titel: Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus
• Verf.angabe: Julia Diegelmann, Florian Beigel, Kathrin Zitzmann, Artur Kaul, Burkhard Göke, Christoph J. Auernhammer, Ralf Bartenschlager, Helmut M. Diepolder, Stephan Brand
• E-Jahr: 2010
• Jahr: December 8, 2010
• Umfang: 13 S.
• Fussnoten: Gesehen am 07.05.2024
• Titel Quelle: Enthalten in: PLOS ONE
• Ort Quelle: San Francisco, California, US : PLOS, 2006
• Jahr Quelle: 2010
• Band/Heft Quelle: 5(2010), 12, Artikel-ID e15200, Seite 1-13
• ISSN Quelle: 1932-6203
• DOI: doi:10.1371/journal.pone.0015200
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Humans
• Sach-SW: Animals
• Sach-SW: Mice
• Sach-SW: Signal Transduction
• Sach-SW: Gene Expression Regulation
• Sach-SW: Leukocytes, Mononuclear
• Sach-SW: Antiviral Agents
• Sach-SW: Interleukins
• Sach-SW: Phosphorylation
• Sach-SW: Transcription, Genetic
• Sach-SW: Liver
• Sach-SW: Hepatitis C
• Sach-SW: Hepacivirus
• Sach-SW: Granulocytes
• Sach-SW: Interferons
• Sach-SW: Muromegalovirus
• Sach-SW: STAT3 Transcription Factor
• K10plus-PPN: 1887973117

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-λ receptor subunits IL-10R2 and IFN-λR1. 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 down-regulated genes). Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. - CONCLUSIONS/SIGNIFICANCE: IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV.