Citation: Yan-zi CHANG, Yan-chang LEI, Wen WU, Shan-shan CHEN, Han-ju HUANG, Dong-liang YANG, Meng-ji LU. Effect of Hepatitis C Virus Core Protein on Interferon-Induced Antiviral Genes Expression and Its Mechanisms .VIROLOGICA SINICA, 2007, 22(5) : 374-379.

Effect of Hepatitis C Virus Core Protein on Interferon-Induced Antiviral Genes Expression and Its Mechanisms

  • Corresponding author: Meng-ji LU, mengji.lu@uni-due.de
  • Received Date: 10 April 2007
    Accepted Date: 08 June 2007
    Available online: 01 October 2007
  • Emerging data indicated that HCV subverts the antiviral activity of interferon (IFN); however, whether HCV core protein contributes to the process remains controversial. In the present study, we examined the effect of HCV core protein on interferon-induced antiviral gene expression and whether the effect is involved in the activation and negative regulation of the Jak/STAT signaling pathway. Our results showed that, following treatment with IFN-α,the transcription of PKR, MxA and 2’-5’OAS were down-regulated in HepG2 cells expressing the core protein. In the presence of HCV core protein, ISRE-dependent luciferase activity also decreased. Further study indicated that the core protein could inhibit the tyrosine phosphorylation of STAT1, whereas the level of STAT1 expression was unchanged. Accordingly, SOCS3, the negative regulator of the Jak/STAT pathway, was induced by HCV core protein. These results suggests that HCV core protein may interfere with the expression of some interferon-induced antiviral genes by inhibiting STAT1 phosphorylation and induction of SOCS3.

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    Effect of Hepatitis C Virus Core Protein on Interferon-Induced Antiviral Genes Expression and Its Mechanisms

      Corresponding author: Meng-ji LU, mengji.lu@uni-due.de
    • 1. Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
    • 2. Division of Clinical Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China

    Abstract: Emerging data indicated that HCV subverts the antiviral activity of interferon (IFN); however, whether HCV core protein contributes to the process remains controversial. In the present study, we examined the effect of HCV core protein on interferon-induced antiviral gene expression and whether the effect is involved in the activation and negative regulation of the Jak/STAT signaling pathway. Our results showed that, following treatment with IFN-α,the transcription of PKR, MxA and 2’-5’OAS were down-regulated in HepG2 cells expressing the core protein. In the presence of HCV core protein, ISRE-dependent luciferase activity also decreased. Further study indicated that the core protein could inhibit the tyrosine phosphorylation of STAT1, whereas the level of STAT1 expression was unchanged. Accordingly, SOCS3, the negative regulator of the Jak/STAT pathway, was induced by HCV core protein. These results suggests that HCV core protein may interfere with the expression of some interferon-induced antiviral genes by inhibiting STAT1 phosphorylation and induction of SOCS3.