SOCS-1 and SOCS-3 inhibit IFN-alpha-induced expression of the antiviral proteins 2,5-OAS and MxA

Biochemical and Biophysical Research Communications
George VlotidesChristoph J Auernhammer

Abstract

Although the use of IFN-alpha in combination with ribavirin has improved the treatment efficacy of chronic hepatitis C virus (HCV) infection, 20-50% of patients still fail to eradicate the virus depending on the HCV genotype. Recently, overexpression of HCV core protein has been shown to inhibit IFN signaling and induce SOCS-3 expression. Aim of this study was to examine the putative role of SOCS proteins in IFN resistance. By Western blot analysis, a 4-fold induction of STAT-1/3 phosphorylation by IFN-alpha was observed in mock-transfected HepG2 clones. In contrast, IFN-induced STAT-1/3 phosphorylation was considerably downregulated by SOCS-1/3 overexpression. In mock-transfected cells, IFN-alpha induced 2',5'-OAS and myxovirus resistance A (MxA) promoter activity 40- to 80-fold and 10- to 35-fold, respectively, and this effect was abrogated in SOCS-1/3 overexpressing cells. As detected by Northern blot technique, IFN-alpha potently induced 2',5'-OAS and MxA mRNA expression in the control clones. Overexpression of SOCS-1 completely abolished both 2',5'-OAS and MxA mRNA expression, whereas SOCS-3 mainly inhibited 2',5'-OAS mRNA expression. Our results demonstrate that SOCS-1 and SOCS-3 proteins inhibit IFN-alpha-induced activat...Continue Reading

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Citations

Sep 27, 2006·Infection and Immunity·Tina Mahieu, Claude Libert
Jul 31, 2013·PloS One·Aideen S CollinsNigel J Stevenson
Oct 7, 2009·Clinical Chemistry and Laboratory Medicine : CCLM·Marcello PersicoAchille Iolascon
Apr 14, 2012·Endocrine-related Cancer·Kathrin ZitzmannChristoph J Auernhammer
Apr 27, 2010·World Journal of Gastroenterology : WJG·Takumi Kawaguchi, Michio Sata
Feb 2, 2012·World Journal of Gastroenterology : WJG·Abdel-Rahman El-Zayadi, Mahmoud Anis
Mar 4, 2014·Hepatology International·Alessandra Mangia, Maria Ripoli
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Apr 10, 2016·Reviews in Medical Virology·Diogo Piedade, José Miguel Azevedo-Pereira
Oct 6, 2016·Inflammation·Elí Terán-Cabanillas, Jesús Hernández
Apr 27, 2005·Biochemical and Biophysical Research Communications·Stephan BrandChristoph J Auernhammer
Sep 1, 2006·Journal of Leukocyte Biology·Niki M MoutsopoulosSharon M Wahl
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Aug 3, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Marcello PersicoAchille Iolascon

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