Protein phosphatase 2A impairs IFNα-induced antiviral activity against the hepatitis C virus through the inhibition of STAT1 tyrosine phosphorylation
- PMID: 23910645
- DOI: 10.1111/jvh.12083
Protein phosphatase 2A impairs IFNα-induced antiviral activity against the hepatitis C virus through the inhibition of STAT1 tyrosine phosphorylation
Abstract
Mammalian cells have developed several mechanisms to sense viruses and initiate adequate responses such as production of interferons. Interferons activate the antiviral response through the Jak-STAT signalling pathway. To establish a chronic infection, viruses need to counteract this barrier of defence. The hepatitis C and hepatitis B viruses are known to up-regulate the expression of protein phosphatase 2A (PP2A). In this study, we show that PP2Ac associates with Jak1/Tyk2/STAT1 and reduces Jak1/Tyk2/STAT1 phosphorylation resulting in an impairment of the IFNα-induced HCV antiviral response. Using the fully infectious HCV cell culture system (HCVcc), we demonstrate that the PP2A catalytic activity is not required to block the antiviral effect of IFNα, although it is needed to support HCVcc replication. Our data suggest an important contribution of virus-induced PP2Ac up-regulation in the establishment of a chronic infection.
Keywords: HCV replication; STAT1; antiviral activity; interferon α; protein phosphatase 2A.
© 2013 John Wiley & Sons Ltd.
Similar articles
-
Hepatitis C virus inhibits interferon signaling through up-regulation of protein phosphatase 2A.Gastroenterology. 2004 Jan;126(1):263-77. doi: 10.1053/j.gastro.2003.10.076. Gastroenterology. 2004. PMID: 14699505
-
Hepatitis B virus polymerase impairs interferon-α-induced STA T activation through inhibition of importin-α5 and protein kinase C-δ.Hepatology. 2013 Feb;57(2):470-82. doi: 10.1002/hep.26064. Hepatology. 2013. PMID: 22996189
-
Inhibition of STAT1 methylation is involved in the resistance of hepatitis B virus to Interferon alpha.Antiviral Res. 2010 Mar;85(3):463-9. doi: 10.1016/j.antiviral.2009.10.011. Epub 2009 Oct 24. Antiviral Res. 2010. PMID: 19857525
-
Suppression of interferon-α signaling by hepatitis E virus.Hepatology. 2012 May;55(5):1324-32. doi: 10.1002/hep.25530. Epub 2012 Apr 4. Hepatology. 2012. PMID: 22183878
-
Activation of STAT1 is required for interferon-alpha-mediated cell death.Exp Cell Res. 2011 Jan 1;317(1):9-19. doi: 10.1016/j.yexcr.2010.10.002. Epub 2010 Oct 16. Exp Cell Res. 2011. PMID: 20937272
Cited by
-
Interplay between Janus Kinase/Signal Transducer and Activator of Transcription Signaling Activated by Type I Interferons and Viral Antagonism.Front Immunol. 2017 Dec 11;8:1758. doi: 10.3389/fimmu.2017.01758. eCollection 2017. Front Immunol. 2017. PMID: 29312301 Free PMC article. Review.
-
B'-protein phosphatase 2A is a functional binding partner of delta-retroviral integrase.Nucleic Acids Res. 2016 Jan 8;44(1):364-76. doi: 10.1093/nar/gkv1347. Epub 2015 Dec 10. Nucleic Acids Res. 2016. PMID: 26657642 Free PMC article.
-
High throughput screen identifies lysosomal acid phosphatase 2 (ACP2) to regulate IFN-1 responses to potentiate oncolytic VSV∆51 activity.Sci Rep. 2024 Nov 16;14(1):28284. doi: 10.1038/s41598-024-76855-3. Sci Rep. 2024. PMID: 39550388 Free PMC article.
-
Viral Inhibition of the IFN-Induced JAK/STAT Signalling Pathway: Development of Live Attenuated Vaccines by Mutation of Viral-Encoded IFN-Antagonists.Vaccines (Basel). 2016 Jun 29;4(3):23. doi: 10.3390/vaccines4030023. Vaccines (Basel). 2016. PMID: 27367734 Free PMC article. Review.
-
The Role of Zinc in Antiviral Immunity.Adv Nutr. 2019 Jul 1;10(4):696-710. doi: 10.1093/advances/nmz013. Adv Nutr. 2019. PMID: 31305906 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous