PKR protein kinase is activated by hepatitis C virus and inhibits viral replication through translational control

Ju Il Kang; Shi Nae Kwon; Se Hoon Park; Yun Ki Kim; Sang Yun Choi; Jungsuh P. Kim; Byung Yoon Ahn

doi:10.1016/j.virusres.2009.01.007

PKR protein kinase is activated by hepatitis C virus and inhibits viral replication through translational control

Ju Il Kang, Shi Nae Kwon, Se Hoon Park, Yun Ki Kim, Sang Yun Choi, Jungsuh P. Kim, Byung Yoon Ahn

Research output: Contribution to journal › Article › peer-review

39 Citations (Scopus)

Abstract

Hepatitis C virus (HCV) infection is currently treated with IFNα-based therapy but little is known how IFNα inhibits HCV replication. We show here that HCV JFH1 infection of human hepatoma Huh-7 cells leads to the activation of IFN-inducible protein kinase PKR and phosphorylation of the translation initiation factor eIF2α. Compared to a control cell HCV replication was significantly elevated in a PKR-knockdown cell, giving rise to a 10-fold higher viral titer, and was less sensitive to IFNα treatment. Conversely, transient expression of PKR inhibited HCV replication in a kinase-dependent manner with concomitant increase of eIF2α phosphorylation. Further, expression of a phospho-mimetic eIF2α mutant moderately inhibited HCV replication. Together, these results demonstrate that PKR is activated by HCV infection and plays a critical antiviral role through inhibition of viral protein translation.

Original language	English
Pages (from-to)	51-56
Number of pages	6
Journal	Virus Research
Volume	142
Issue number	1-2
DOIs	https://doi.org/10.1016/j.virusres.2009.01.007
Publication status	Published - 2009 Jun

Bibliographical note

Funding Information:
We thank T. Wakita for kindly providing us with pJFH1. This work was supported by the 21C Frontier Grant for Functional Human Genome Research (FG08-21-22) from the Ministry of Science and Technology of Korea. J.I. Kang, S.N. Kwon, and S.H. Park were supported by the BK21 Graduate Scholarship Program from the Ministry of Education of Korea. J.P. Kim was supported by the Brain Pool program (041S-4-8) of MST of Korea.

Keywords

Hepatitis C virus
Interferon
JFH1
PKR
Translational control
eIF2α phosphorylation

ASJC Scopus subject areas

Virology
Infectious Diseases
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.virusres.2009.01.007

Cite this

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title = "PKR protein kinase is activated by hepatitis C virus and inhibits viral replication through translational control",

abstract = "Hepatitis C virus (HCV) infection is currently treated with IFNα-based therapy but little is known how IFNα inhibits HCV replication. We show here that HCV JFH1 infection of human hepatoma Huh-7 cells leads to the activation of IFN-inducible protein kinase PKR and phosphorylation of the translation initiation factor eIF2α. Compared to a control cell HCV replication was significantly elevated in a PKR-knockdown cell, giving rise to a 10-fold higher viral titer, and was less sensitive to IFNα treatment. Conversely, transient expression of PKR inhibited HCV replication in a kinase-dependent manner with concomitant increase of eIF2α phosphorylation. Further, expression of a phospho-mimetic eIF2α mutant moderately inhibited HCV replication. Together, these results demonstrate that PKR is activated by HCV infection and plays a critical antiviral role through inhibition of viral protein translation.",

keywords = "Hepatitis C virus, Interferon, JFH1, PKR, Translational control, eIF2α phosphorylation",

author = "Kang, {Ju Il} and Kwon, {Shi Nae} and Park, {Se Hoon} and Kim, {Yun Ki} and Choi, {Sang Yun} and Kim, {Jungsuh P.} and Ahn, {Byung Yoon}",

note = "Funding Information: We thank T. Wakita for kindly providing us with pJFH1. This work was supported by the 21C Frontier Grant for Functional Human Genome Research (FG08-21-22) from the Ministry of Science and Technology of Korea. J.I. Kang, S.N. Kwon, and S.H. Park were supported by the BK21 Graduate Scholarship Program from the Ministry of Education of Korea. J.P. Kim was supported by the Brain Pool program (041S-4-8) of MST of Korea.",

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doi = "10.1016/j.virusres.2009.01.007",

language = "English",

volume = "142",

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issn = "0168-1702",

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AU - Kang, Ju Il

AU - Kwon, Shi Nae

AU - Park, Se Hoon

AU - Kim, Yun Ki

AU - Choi, Sang Yun

AU - Kim, Jungsuh P.

AU - Ahn, Byung Yoon

N1 - Funding Information: We thank T. Wakita for kindly providing us with pJFH1. This work was supported by the 21C Frontier Grant for Functional Human Genome Research (FG08-21-22) from the Ministry of Science and Technology of Korea. J.I. Kang, S.N. Kwon, and S.H. Park were supported by the BK21 Graduate Scholarship Program from the Ministry of Education of Korea. J.P. Kim was supported by the Brain Pool program (041S-4-8) of MST of Korea.

PY - 2009/6

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N2 - Hepatitis C virus (HCV) infection is currently treated with IFNα-based therapy but little is known how IFNα inhibits HCV replication. We show here that HCV JFH1 infection of human hepatoma Huh-7 cells leads to the activation of IFN-inducible protein kinase PKR and phosphorylation of the translation initiation factor eIF2α. Compared to a control cell HCV replication was significantly elevated in a PKR-knockdown cell, giving rise to a 10-fold higher viral titer, and was less sensitive to IFNα treatment. Conversely, transient expression of PKR inhibited HCV replication in a kinase-dependent manner with concomitant increase of eIF2α phosphorylation. Further, expression of a phospho-mimetic eIF2α mutant moderately inhibited HCV replication. Together, these results demonstrate that PKR is activated by HCV infection and plays a critical antiviral role through inhibition of viral protein translation.

AB - Hepatitis C virus (HCV) infection is currently treated with IFNα-based therapy but little is known how IFNα inhibits HCV replication. We show here that HCV JFH1 infection of human hepatoma Huh-7 cells leads to the activation of IFN-inducible protein kinase PKR and phosphorylation of the translation initiation factor eIF2α. Compared to a control cell HCV replication was significantly elevated in a PKR-knockdown cell, giving rise to a 10-fold higher viral titer, and was less sensitive to IFNα treatment. Conversely, transient expression of PKR inhibited HCV replication in a kinase-dependent manner with concomitant increase of eIF2α phosphorylation. Further, expression of a phospho-mimetic eIF2α mutant moderately inhibited HCV replication. Together, these results demonstrate that PKR is activated by HCV infection and plays a critical antiviral role through inhibition of viral protein translation.

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KW - Interferon

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KW - Translational control

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PKR protein kinase is activated by hepatitis C virus and inhibits viral replication through translational control

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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