The modulation of hepatitis C virus 1a replication by PKR is dependent on NF-kB mediated interferon beta response in Huh7.5.1 cells

Lumin Zhang, Harvey J. Alter, Haiping Wang, Shuaizheng Jia, Ena Wang, Francesco M. Marincola, James W K Shih, Richard Y. Wang

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Protein kinase R (PKR), a sensor of double-stranded RNA, plays an important role in the host response to viral infection. Hepatitis C genotype 2a virus (HCV2a) has been shown to induce PKR activation to suppress the translation of antiviral interferon stimulated genes (ISGs), suggesting that PKR inhibitor can be beneficial for treating chronically HCV-infected patients in conjunction with interferon alpha and ribavirin. However, in this study, we found that PKR inhibition using siRNA PKR, shRNA PKR or PKR inhibitor enhanced HCV 1a replication and rendered Huh7.5.1 cells more susceptible to HCV1a infection. Additionally, PKR silencing suppressed NF-kB activation and NF-kB mediated STAT1 phosphorylation in Huh7.5.1 cells and HCV1a persistently infected Huh7.5.1 cells (2HDD4). These effects were accompanied by a reduction of interferon beta response and thereby enhanced HCV1a replication in Huh7.5.1 cells. We conclude that host cells can employ PKR activation to restrict HCV1a replication through regulation of NF-kB expression.

Original languageEnglish
Pages (from-to)28-36
Number of pages9
JournalVirology
Volume438
Issue number1
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

NF-kappa B
Interferon-beta
Virus Replication
Hepacivirus
Protein Kinases
Protein Kinase Inhibitors
Small Interfering RNA
Double-Stranded RNA
Ribavirin
Virus Diseases
Hepatitis C
Interferon-alpha
Interferons
Antiviral Agents
Genotype
Phosphorylation
Viruses
Infection
Proteins

Keywords

  • HCV1a replication
  • IFN-Β
  • NF-kB activation
  • PKR silencing

ASJC Scopus subject areas

  • Virology

Cite this

The modulation of hepatitis C virus 1a replication by PKR is dependent on NF-kB mediated interferon beta response in Huh7.5.1 cells. / Zhang, Lumin; Alter, Harvey J.; Wang, Haiping; Jia, Shuaizheng; Wang, Ena; Marincola, Francesco M.; Shih, James W K; Wang, Richard Y.

In: Virology, Vol. 438, No. 1, 2013, p. 28-36.

Research output: Contribution to journalArticle

Zhang, Lumin ; Alter, Harvey J. ; Wang, Haiping ; Jia, Shuaizheng ; Wang, Ena ; Marincola, Francesco M. ; Shih, James W K ; Wang, Richard Y. / The modulation of hepatitis C virus 1a replication by PKR is dependent on NF-kB mediated interferon beta response in Huh7.5.1 cells. In: Virology. 2013 ; Vol. 438, No. 1. pp. 28-36.
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