Adenovirus-mediated gene transfer of interferon α inhibits hepatitis C virus replication in hepatocytes

Koichi Suzuki, Kazunori Aoki, Shumpei Ohnami, Kimiko Yoshida, Teruhisa Kazui, Nobuyuki Kato, Kazuaki Inoue, Michinori Kohara, Teruhiko Yoshida

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Recently we reported that on-site interferon (IFN)-α production in the liver using an adenovirus vector can achieve a substantial confinement of IFN-α in the target organ and can improve liver fibrosis in a rat liver cirrhosis model. However, the major therapeutic effect of IFN for hepatitis C virus (HCV)-associated liver diseases is its antiviral effect on HCV. As a prelude to the in vivo HCV infection experiment using a primate animal model, here we examined the antiviral effect of IFN-α gene transfer into HCV-positive hepatocytes in vitro. The non-neoplastic human hepatocyte cell line PH5CH8 was inoculated with HCV-positive serum. Successful in vitro HCV replication and thus the validity of this model was confirmed by a strong selection for HCV variants determined by sequence analysis of the hypervariable region and an increase of HCV RNA estimated by real time TaqMan RT-PCR. One day after the inoculation of HCV, PH5CH8 cells were infected with adenoviral vectors encoding human IFN-α cDNA. HCV completely disappeared 9 days after the adenoviral infection, which is linked to the increase of 2,5-oligoadenylate synthetase activity, suggesting that IFN-α produced by gene transfer effectively inhibits HCV replication in hepatocytes. This study supports the development of IFN-α gene therapy for HCV-associated liver diseases.

Original languageEnglish
Pages (from-to)814-819
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume307
Issue number4
DOIs
Publication statusPublished - Aug 8 2003

Keywords

  • Adenovirus
  • Gene transfer
  • Hepatitis C virus
  • Interferon
  • Liver cirrhosis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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