The NS5A protein of hepatitis C virus represses gene expression of hRPB10α, a common subunit of host RNA polymerases, through interferon regulatory factor-1 binding site

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Title
The NS5A protein of hepatitis C virus represses gene expression of hRPB10α, a common subunit of host RNA polymerases, through interferon regulatory factor-1 binding site
Author(s)
Cho-Rok Jung; See Young Choi; Dong Soo Im
Bibliographic Citation
Virus Research, vol. 129, no. 2, pp. 155-165
Publication Year
2007
Abstract
The nonstructural (NS) 5A protein of hepatitis C virus (HCV) plays important roles in both viral RNA replication and modulation of the physiology of the host cell. Here we report that NS5A repressed gene expression of hRPB10α, a common subunit of host RNA polymerases (Pol), in hepatoma cell lines and Huh-7 cells harboring HCV replicon. Analysis of the hRPB10α promoter region revealed that interferon regulatory factor-1 binding element (IRF-E) was essential for its transcription. The IRF-E was responsible for the NS5A-mediated repression of the hRPB10α transcription and its induction by IRF-1 that is known to be induced by interferon-α. Electrophoretic mobility shift assay showed that IRF-1 bound to the IRF-E and the binding reduced when NS5A was expressed. NS5A appeared to negatively regulate IRF-1 expression, which might be partly responsible for the decrease of hRPB10α expression. NS5A expression moderately decreased promoter-independent Pol activity in vitro. Transcription of adenoviral genes that are dependent on Pol II or III and propagation of adenoviral genome were impaired in HeLa cells with stable NS5A expression. The results suggest that NS5A may partly modulate host cell transcription by the down-regulation of hRPB10α.
Keyword
HCVhost RNA polymerasehRPB10αinterferon-αIRF-1IRF-ENS5A
ISSN
0168-1702
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.virusres.2007.07.005
Type
Article
Appears in Collections:
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
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