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KMID : 0620920160480110006
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Experimental & Molecular Medicine
2016 Volume.48 No. 11 p.6 ~ p.6
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Immunoproteasome induction is suppressed in hepatitis C virus-infected cells in a protein kinase R-dependent manner
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Oh In-Soo
Kathrin Textoris-Taube
Sung Pil-Soo
Kang Won-Seok
Xenia Gorny
Thilo Kahne
Hong Seon-Hui
Choi Young-Joon
Clemens Cammann
Michael Naumann
Kim Jong-Hoon
Park Su-Hyung
Yoo Ook-Joon
Peter M Kloetzel
Ulrike Seifert
Shin Eui-Cheol
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Abstract
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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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