PKR-dependent mechanisms of interferon-a for inhibiting hepatitis B virus replication

Il Hyun Park; Kyung Won Baek; Eun Young Cho; Byung Yoon Ahn

doi:10.1007/s10059-011-1059-6

PKR-dependent mechanisms of interferon-a for inhibiting hepatitis B virus replication

Il Hyun Park, Kyung Won Baek, Eun Young Cho, Byung Yoon Ahn

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

25 Citations (Scopus)

Abstract

Interferon-a (IFN-a) inhibits the replication of hepatitis B virus (HBV) in vivo and in vitro, but the molecular mechanism of this inhibition has been elusive. We found that while HBV replication in transfected human hepatoma Huh-7 cell was severely inhibited by IFN-a treatment as reported previously, this inhibition was markedly impaired in the cell in which the expression of IFN-inducible, double- stranded RNA-dependent protein kinase (PKR) was stably and specifically suppressed through RNA-interference. Intracellular level of viral capsids was down-regulated likewise in a PKR-dependent manner, whereas that of HBV transcripts including the viral RNA pregenome was not affected by IFN-a treatment. Ectopic expression of PKR also resulted in the reduction of viral capsids with concomitant increase of phosphorylated eIF2a. These results suggested that PKR functions as a key mediator of IFN-a in opposing HBV replication, most likely through the inhibition of protein synthesis.

Original language	English
Pages (from-to)	167-172
Number of pages	6
Journal	Molecules and cells
Volume	32
Issue number	2
DOIs	https://doi.org/10.1007/s10059-011-1059-6
Publication status	Published - 2011 Aug

Bibliographical note

Funding Information:
We thank W.S. Ryu for kindly p roviding us with p HBV1.2. This work was sup p orted by the Health Technology Research Grant (#A080599) from the Ministry of Health, Welfare and Family Affairs of the Rep ublic of Korea.

Keywords

Antiviral mechanism
Hepatitis B virus
IFN-a
PKR

ASJC Scopus subject areas

Molecular Biology
Cell Biology

UN SDGs

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

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10.1007/s10059-011-1059-6

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title = "PKR-dependent mechanisms of interferon-a for inhibiting hepatitis B virus replication",

abstract = "Interferon-a (IFN-a) inhibits the replication of hepatitis B virus (HBV) in vivo and in vitro, but the molecular mechanism of this inhibition has been elusive. We found that while HBV replication in transfected human hepatoma Huh-7 cell was severely inhibited by IFN-a treatment as reported previously, this inhibition was markedly impaired in the cell in which the expression of IFN-inducible, double- stranded RNA-dependent protein kinase (PKR) was stably and specifically suppressed through RNA-interference. Intracellular level of viral capsids was down-regulated likewise in a PKR-dependent manner, whereas that of HBV transcripts including the viral RNA pregenome was not affected by IFN-a treatment. Ectopic expression of PKR also resulted in the reduction of viral capsids with concomitant increase of phosphorylated eIF2a. These results suggested that PKR functions as a key mediator of IFN-a in opposing HBV replication, most likely through the inhibition of protein synthesis.",

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author = "Park, {Il Hyun} and Baek, {Kyung Won} and Cho, {Eun Young} and Ahn, {Byung Yoon}",

note = "Funding Information: We thank W.S. Ryu for kindly p roviding us with p HBV1.2. This work was sup p orted by the Health Technology Research Grant (#A080599) from the Ministry of Health, Welfare and Family Affairs of the Rep ublic of Korea.",

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AU - Baek, Kyung Won

AU - Cho, Eun Young

AU - Ahn, Byung Yoon

N1 - Funding Information: We thank W.S. Ryu for kindly p roviding us with p HBV1.2. This work was sup p orted by the Health Technology Research Grant (#A080599) from the Ministry of Health, Welfare and Family Affairs of the Rep ublic of Korea.

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N2 - Interferon-a (IFN-a) inhibits the replication of hepatitis B virus (HBV) in vivo and in vitro, but the molecular mechanism of this inhibition has been elusive. We found that while HBV replication in transfected human hepatoma Huh-7 cell was severely inhibited by IFN-a treatment as reported previously, this inhibition was markedly impaired in the cell in which the expression of IFN-inducible, double- stranded RNA-dependent protein kinase (PKR) was stably and specifically suppressed through RNA-interference. Intracellular level of viral capsids was down-regulated likewise in a PKR-dependent manner, whereas that of HBV transcripts including the viral RNA pregenome was not affected by IFN-a treatment. Ectopic expression of PKR also resulted in the reduction of viral capsids with concomitant increase of phosphorylated eIF2a. These results suggested that PKR functions as a key mediator of IFN-a in opposing HBV replication, most likely through the inhibition of protein synthesis.

AB - Interferon-a (IFN-a) inhibits the replication of hepatitis B virus (HBV) in vivo and in vitro, but the molecular mechanism of this inhibition has been elusive. We found that while HBV replication in transfected human hepatoma Huh-7 cell was severely inhibited by IFN-a treatment as reported previously, this inhibition was markedly impaired in the cell in which the expression of IFN-inducible, double- stranded RNA-dependent protein kinase (PKR) was stably and specifically suppressed through RNA-interference. Intracellular level of viral capsids was down-regulated likewise in a PKR-dependent manner, whereas that of HBV transcripts including the viral RNA pregenome was not affected by IFN-a treatment. Ectopic expression of PKR also resulted in the reduction of viral capsids with concomitant increase of phosphorylated eIF2a. These results suggested that PKR functions as a key mediator of IFN-a in opposing HBV replication, most likely through the inhibition of protein synthesis.

KW - Antiviral mechanism

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PKR-dependent mechanisms of interferon-a for inhibiting hepatitis B virus replication

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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