論文

査読有り 国際誌
2019年3月

Activation of protein kinase R by hepatitis C virus RNA-dependent RNA polymerase.

Virology
  • Ryosuke Suzuki
  • ,
  • Mami Matsuda
  • ,
  • Takashi Shimoike
  • ,
  • Koichi Watashi
  • ,
  • Hideki Aizaki
  • ,
  • Takanobu Kato
  • ,
  • Tetsuro Suzuki
  • ,
  • Masamichi Muramatsu
  • ,
  • Takaji Wakita

529
開始ページ
226
終了ページ
233
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.virol.2019.01.024

Hepatitis C virus (HCV) was shown to activate protein kinase R (PKR), which inhibits expression of interferon (IFN) and IFN-stimulated genes by controlling the translation of newly transcribed mRNAs. However, it is unknown exactly how HCV activates PKR. To address the molecular mechanism(s) of PKR activation mediated by HCV infection, we examined the effects of viral proteins on PKR activation. Here, we show that expression of HCV NS5B strongly induced PKR and eIF2α phosphorylation, and attenuated MHC class I expression. In contrast, expression of Japanese encephalitis virus RNA-dependent RNA polymerase did not induce phosphorylation of PKR. Co-immunoprecipitation analyses showed that HCV NS5B interacted with PKR. Furthermore, expression of NS5B with polymerase activity-deficient mutation failed to phosphorylate PKR, suggesting that RNA polymerase activity is required for PKR activation. These results suggest that HCV activates PKR by association with NS5B, resulting in translational suppression of MHC class I to establish chronic infection.

リンク情報
DOI
https://doi.org/10.1016/j.virol.2019.01.024
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30738360

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