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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

Authors 

Cho-Rok JungSee Young ChoiDong Soo Im

Publisher 

Elsevier

Issue Date 

2007

Citation 

Virus Research, vol. 129, no. 2, pp. 155-165

Keywords 

HCVhost RNA polymerasehRPB10αinterferon-αIRF-1IRF-ENS5Aalpha interferoninterferon regulatory factor 1nonstructural protein 5A

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.

ISSN 

0168-1702

Link 

http://dx.doi.org/10.1016/j.virusres.2007.07.005

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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