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Immunoproteasome induction is suppressed in hepatitis C virus-infected cells in a protein kinase R-dependent manner

 In Soo Oh  ;  Kathrin Textoris-Taube  ;  Pil Soo Sung  ;  Wonseok Kang  ;  Xenia Gorny  ;  Thilo Kähne  ;  Seon-Hui Hong  ;  Young Joon Choi  ;  Clemens Cammann  ;  Michael Naumann  ;  Jong Hoon Kim  ;  Su-Hyung Park  ;  Ook Joon Yoo  ;  Peter M Kloetzel  ;  Ulrike Seifert  ;  Eui-Cheol Shin 
 Experimental and Molecular Medicine, Vol.48(11) : e270, 2016 
Journal Title
 Experimental and Molecular Medicine 
Issue Date
By changing the relative abundance of generated antigenic peptides through alterations in the proteolytic activity, interferon (IFN)-γ-induced immunoproteasomes influence the outcome of CD8+ cytotoxic T lymphocyte responses. In the present study, we investigated the effects of hepatitis C virus (HCV) infection on IFN-γ-induced immunoproteasome expression using a HCV infection cell culture system. We found that, although IFN-γ induced the transcriptional expression of mRNAs encoding the β1i/LMP2, β2i/MECL-1 and β5i/LMP7 immunoproteasome subunits, the formation of immunoproteasomes was significantly suppressed in HCV-infected cells. This finding indicated that immunoproteasome induction was impaired at the translational or posttranslational level by HCV infection. Gene silencing studies showed that the suppression of immunoproteasome induction is essentially dependent on protein kinase R (PKR). Indeed, the generation of a strictly immunoproteasome-dependent cytotoxic T lymphocyte epitope was impaired in in vitro processing experiments using isolated 20S proteasomes from HCV-infected cells and was restored by the silencing of PKR expression. In conclusion, our data point to a novel mechanism of immune regulation by HCV that affects the antigen-processing machinery through the PKR-mediated suppression of immunoproteasome induction in infected cells.
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1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
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김종훈(Kim, Jong Hoon) ORCID logo https://orcid.org/0000-0002-3385-8180
최영준(Choi, Young Joon)
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