Journal
VIROLOGY
Volume 346, Issue 2, Pages 348-362Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2005.10.023
Keywords
hepatitis C virus; NS5B; interferon-beta; TLR3; hepatocyte cells
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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)-beta neutralizing antibody restored the cell cycle delay, IFN-beta was deemed responsible for the cell cycle delay in NS5B-expressing PH5CH8 cells. The induction of IFN-beta 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-beta, and the activation of the IFN-beta signaling pathway. Our findings revealed that NS5B induced IFN-beta through the TLR3 signaling pathway in immortalized human hepatocytes even without replicating viral genomes. (C) 2005 Elsevier Inc. All rights reserved.
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