Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus
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 propertie...
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| Hauptverfasser: | , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
December 8, 2010
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| In: |
PLOS ONE
Year: 2010, Jahrgang: 5, Heft: 12, Pages: 1-13 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0015200 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1371/journal.pone.0015200
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| Verfasserangaben: | Julia Diegelmann, Florian Beigel, Kathrin Zitzmann, Artur Kaul, Burkhard Göke, Christoph J. Auernhammer, Ralf Bartenschlager, Helmut M. Diepolder, Stephan Brand |
MARC
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| 245 | 1 | 0 | |a Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus |c Julia Diegelmann, Florian Beigel, Kathrin Zitzmann, Artur Kaul, Burkhard Göke, Christoph J. Auernhammer, Ralf Bartenschlager, Helmut M. Diepolder, Stephan Brand |
| 264 | 1 | |c December 8, 2010 | |
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| 520 | |a 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. | ||
| 650 | 4 | |a Humans | |
| 650 | 4 | |a Animals | |
| 650 | 4 | |a Mice | |
| 650 | 4 | |a Signal Transduction | |
| 650 | 4 | |a Gene Expression Regulation | |
| 650 | 4 | |a Leukocytes, Mononuclear | |
| 650 | 4 | |a Antiviral Agents | |
| 650 | 4 | |a Interleukins | |
| 650 | 4 | |a Phosphorylation | |
| 650 | 4 | |a Transcription, Genetic | |
| 650 | 4 | |a Liver | |
| 650 | 4 | |a Hepatitis C | |
| 650 | 4 | |a Hepacivirus | |
| 650 | 4 | |a Granulocytes | |
| 650 | 4 | |a Interferons | |
| 650 | 4 | |a Muromegalovirus | |
| 650 | 4 | |a STAT3 Transcription Factor | |
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| 700 | 1 | |a Brand, Stephan |e VerfasserIn |4 aut | |
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