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

Abstract:

: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.

journal_name

Virology

journal_title

Virology

authors

Suzuki R,Matsuda M,Shimoike T,Watashi K,Aizaki H,Kato T,Suzuki T,Muramatsu M,Wakita T

doi

10.1016/j.virol.2019.01.024

subject

Has Abstract

pub_date

2019-03-01 00:00:00

pages

226-233

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(19)30028-5

journal_volume

529

pub_type

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