SOCS-1 inhibits expression of the antiviral proteins 2',5'-OAS and MxA induced by the novel interferon-lambdas IL-28A and IL-29

Stephan Brand; Kathrin Zitzmann; Julia Dambacher; Florian Beigel; Torsten Olszak; George Vlotides; Sören T Eichhorst; Burkhard Göke; Helmut Diepolder; Christoph J Auernhammer

doi:10.1016/j.bbrc.2005.04.004

SOCS-1 inhibits expression of the antiviral proteins 2',5'-OAS and MxA induced by the novel interferon-lambdas IL-28A and IL-29

Biochem Biophys Res Commun. 2005 Jun 3;331(2):543-8. doi: 10.1016/j.bbrc.2005.04.004.

Authors

Stephan Brand¹, Kathrin Zitzmann, Julia Dambacher, Florian Beigel, Torsten Olszak, George Vlotides, Sören T Eichhorst, Burkhard Göke, Helmut Diepolder, Christoph J Auernhammer

Affiliation

¹ Department of Medicine II, University-Hospital Munich-Grosshadern, University of Munich, Germany. stepha.brand@med.uni-muenchen.de

PMID: 15850793
DOI: 10.1016/j.bbrc.2005.04.004

Abstract

Recently, we have shown that SOCS-1/3 overexpression in hepatic cells abrogates signaling of type I interferons (IFN) which may contribute to the frequently observed IFN resistance of hepatitis C virus (HCV). IFN-lambdas (IL-28A/B and IL-29), a novel group of IFNs, also efficiently inhibit HCV replication in vitro with potentially less hematopoietic side effects than IFN-alpha because of limited receptor expression in hematopoietic cells. To further evaluate the potential of IFN-lambdas in chronic viral hepatitis, we examined the influence of SOCS protein expression on IFN-lambda signaling. First, we show that hepatic cell lines express the IFN-lambda receptor complex consisting of IFN-lambdaR1 (IL-28R1) and IL-10R2. Whereas in mock-transfected HepG2 cells, IL-28A and IL-29 induced STAT1 and STAT3 phosphorylation, overexpression of SOCS-1 completely abrogated IL-28A and IL-29-induced STAT1/3 phosphorylation. Similarly, IL-28A and IL-29 induced mRNA expression of the antiviral proteins 2',5'-OAS and MxA was abolished by overexpression of SOCS-1. In conclusion, we assume that despite antiviral properties of IFN-lambdas, their efficacy as antiviral agents may have similar limitations as IFN-alpha due to inhibition by SOCS proteins.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

2',5'-Oligoadenylate Synthetase / genetics
2',5'-Oligoadenylate Synthetase / metabolism*
Antiviral Agents / metabolism
Cell Line, Tumor
Cytokines
DNA-Binding Proteins / metabolism
GTP-Binding Proteins / genetics
GTP-Binding Proteins / metabolism*
Gene Expression
Gene Expression Regulation*
Hepatitis C, Chronic / immunology
Hepatitis C, Chronic / metabolism
Hepatitis C, Chronic / virology
Humans
Interferons / chemistry
Interferons / genetics
Interferons / immunology
Interferons / metabolism*
Interleukins / genetics
Interleukins / immunology
Interleukins / metabolism*
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / metabolism*
Myxovirus Resistance Proteins
Phosphorylation
Phosphotyrosine / metabolism
Repressor Proteins / genetics
Repressor Proteins / metabolism*
STAT1 Transcription Factor
STAT3 Transcription Factor
Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling Proteins
Trans-Activators / metabolism

Substances

Antiviral Agents
Cytokines
DNA-Binding Proteins
interferon-lambda, human
Interleukins
Intracellular Signaling Peptides and Proteins
MX1 protein, human
Myxovirus Resistance Proteins
Repressor Proteins
SOCS1 protein, human
STAT1 Transcription Factor
STAT1 protein, human
STAT3 Transcription Factor
STAT3 protein, human
Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling Proteins
Trans-Activators
Phosphotyrosine
Interferons
OAS1 protein, human
2',5'-Oligoadenylate Synthetase
GTP-Binding Proteins