Activation of protein kinase R by hepatitis C virus RNA-dependent RNA polymerase
Autor: | Tetsuro Suzuki, Hideki Aizaki, Takanobu Kato, Masamichi Muramatsu, Koichi Watashi, Mami Matsuda, Takashi Shimoike, Takaji Wakita, Ryosuke Suzuki |
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Rok vydání: | 2019 |
Předmět: |
Gene Expression Regulation
Viral Carcinoma Hepatocellular viruses Hepatitis C virus Hepacivirus medicine.disease_cause environment and public health Virus eIF-2 Kinase 03 medical and health sciences chemistry.chemical_compound Interferon Cell Line Tumor Virology RNA polymerase MHC class I medicine Humans NS5B Polymerase 030304 developmental biology 0303 health sciences biology Liver Neoplasms 030302 biochemistry & molecular biology virus diseases biochemical phenomena metabolism and nutrition RNA-Dependent RNA Polymerase Protein kinase R Enzyme Activation Gene Expression Regulation Neoplastic enzymes and coenzymes (carbohydrates) chemistry biology.protein RNA Viral Plasmids medicine.drug |
Zdroj: | Virology. 529:226-233 |
ISSN: | 0042-6822 |
Popis: | 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. |
Databáze: | OpenAIRE |
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