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Hepatitis C virus (HCV) NS2 protein up-regulates HCV IRES-dependent translation and down-regulates NS5B RdRp activity

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Abstract

Chronic hepatitis C virus (HCV) infection often leads to liver cancer. The HCV NS2 protein is a hydrophobic transmembrane protein that associates with several cellular proteins in mammalian cells. In this report, we investigated the function of NS2 protein on HCV replication and translation by using a transient cell-based expression system. Cells co-transfected with pcDNA3.1 (−)-NS2 and the dual-luciferase reporter construct containing the HCV IRES were used to detect the effect of NS2 protein on HCV translation. Cells co-transfected with pcDNA3.1(−)-NS2, pcDNA-NS5B and a reporter plasmid were used to detect the effect of NS2 protein on HCV replication. The results showed that HCV NS2 protein up-regulated HCV IRES-dependent translation in a specific and dose-dependent manner in Huh7 cells but not in HeLa and HepG2 cells, and NS2 protein inhibited NS5B RdRp activity in a dose-independent manner in all three cell lines. These findings may suggest a novel mechanism by which HCV modulates its NS5B replication and IRES-dependent translation and facilitates virus persistence.

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Acknowledgments

We thank Michael G. Katze from the University of Washington for providing the dual-luciferase reporter constructs containing the HCV IRES, the poliovirus IRES and the encephalomyocarditis (EMCV) IRES. We thank Guangxiang Luo from the University of Kentucky for providing the plasmid pUC/HCV 3′UTR.

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Authors and Affiliations

  1. State Key Laboratory of Virology, College of Life Science, Wuhan Univerisity, 430072, Wuhan, Hubei, People’s Republic of China

    Yinglong She, Linbai Ye & Zhenghui Wu

  2. State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academic of Science, 430071, Wuhan, Hubei, People’s Republic of China

    Qingjiao Liao & Xulin Chen

Authors
  1. Yinglong She
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  2. Qingjiao Liao
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  3. Xulin Chen
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  4. Linbai Ye
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  5. Zhenghui Wu
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Corresponding author

Correspondence to Linbai Ye.

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Y. She and Q. Liao contributed equally to this work.

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She, Y., Liao, Q., Chen, X. et al. Hepatitis C virus (HCV) NS2 protein up-regulates HCV IRES-dependent translation and down-regulates NS5B RdRp activity. Arch Virol 153, 1991–1997 (2008). https://doi.org/10.1007/s00705-008-0198-3

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  • DOI: https://doi.org/10.1007/s00705-008-0198-3

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