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...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
December 8, 2010
|
| In: |
PLOS ONE
Year: 2010, Volume: 5, Issue: 12, Pages: 1-13 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0015200 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1371/journal.pone.0015200
|
| Author Notes: | Julia Diegelmann, Florian Beigel, Kathrin Zitzmann, Artur Kaul, Burkhard Göke, Christoph J. Auernhammer, Ralf Bartenschlager, Helmut M. Diepolder, Stephan Brand |
| Summary: | 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. |
|---|---|
| Item Description: | Gesehen am 07.05.2024 |
| Physical Description: | Online Resource |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0015200 |