Immunoproteasome induction is suppressed in hepatitis C virus-infected cells in a protein kinase R-dependent manner
- Authors
- Oh, In Soo; Textoris-Taube, Kathrin; Sung, Pil Soo; Kang, Wonseok; Gorny, Xenia; Kaehne, Thilo; Hong, Seon-Hui; Choi, Young Joon; Cammann, Clemens; Naumann, Michael; Kim, Jong Hoon; Park, Su-Hyung; Yoo, Ook Joon; Kloetzel, Peter M.; Seifert, Ulrike; Shin, Eui-Cheol
- Issue Date
- Nov-2016
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- EXPERIMENTAL AND MOLECULAR MEDICINE, v.48, no.11
- Journal Title
- EXPERIMENTAL AND MOLECULAR MEDICINE
- Volume
- 48
- Number
- 11
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/64133
- DOI
- 10.1038/emm.2016.98
- ISSN
- 1226-3613
2092-6413
- Abstract
- By changing the relative abundance of generated antigenic peptides through alterations in the proteolytic activity, interferon (IFN)-gamma-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-gamma-induced immunoproteasome expression using a HCV infection cell culture system. We found that, although IFN-gamma induced the transcriptional expression of mRNAs encoding the beta 1i/LMP2, beta 2i/MECL-1 and beta 5i/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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