title: The modulation of hepatitis C virus 1a replication by PKR is dependent on NF-kB mediated interferon beta response in Huh7.5.1 cells.
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.
authors: Infectious Disease and Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Lumin
authors: L
authors: Zhang
authors: Harvey J
authors: HJ
authors: Alter
authors: Haiping
authors: H
authors: Wang
authors: Shuaizheng
authors: S
authors: Jia
authors: Ena
authors: E
authors: Wang
authors: Francesco M
authors: FM
authors: Marincola
authors: James W-K
authors: JW
authors: Shih
authors: Richard Y
authors: RY
authors: Wang
mesh_terms: D002460:Cell Line; D020868:Gene Silencing; D016174:Hepacivirus / Q000472:pathogenicity / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D014779:Virus Replication; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D016899:Interferon-beta; D019892:eIF-2 Kinase
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