Hepatitis C virus NS5B delays cell cycle progression by inducing interferon-β via Toll-like receptor 3 signaling pathway without replicating viral genomes

Kazuhito Naka, Hiromichi Dansako, Naoya Kobayashi, Masanori Ikeda, Nobuyuki Kato

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

To clarify the pathogenesis of hepatitis C virus (HCV), we have studied the effects of HCV proteins using human hepatocytes. Here, we found that HCV NS5B, an RNA-dependent RNA polymerase, delayed cell cycle progression through the S phase in PH5CH8 immortalized human hepatocyte cells. Since treatment with anti-interferon (IFN)-β neutralizing antibody restored the cell cycle delay, IFN-β was deemed responsible for the cell cycle delay in NS5B-expressing PH5CH8 cells. The induction of IFN-β and the cell cycle delay were overridden by the down-regulation of Toll-like receptor 3 (TLR3) through RNA interference in NS5B-expressing PH5CH8 cells. Moreover, the NS5B full form was required for the cell cycle delay, the induction of IFN-β, and the activation of the IFN-β signaling pathway. Our findings revealed that NS5B induced IFN-β through the TLR3 signaling pathway in immortalized human hepatocytes even without replicating viral genomes.

Original languageEnglish
Pages (from-to)348-362
Number of pages15
JournalVirology
Volume346
Issue number2
DOIs
Publication statusPublished - Mar 15 2006

Keywords

  • Hepatitis C virus
  • Hepatocyte cells
  • Interferon-β
  • NS5B
  • TLR3

ASJC Scopus subject areas

  • Virology

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