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 journalArticle

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

Fingerprint

Gene transfer
Virus Replication
Viruses
Adenoviridae
Hepacivirus
Interferons
Hepatocytes
Genes
Liver
Liver Cirrhosis
Antiviral Agents
Liver Diseases
Gene therapy
Therapeutic Uses
Virus Diseases
Ligases
Genetic Therapy
Primates
Sequence Analysis
Rats

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Adenovirus-mediated gene transfer of interferon α inhibits hepatitis C virus replication in hepatocytes. / Suzuki, Koichi; Aoki, Kazunori; Ohnami, Shumpei; Yoshida, Kimiko; Kazui, Teruhisa; Kato, Nobuyuki; Inoue, Kazuaki; Kohara, Michinori; Yoshida, Teruhiko.

In: Biochemical and Biophysical Research Communications, Vol. 307, No. 4, 08.08.2003, p. 814-819.

Research output: Contribution to journalArticle

Suzuki, Koichi ; Aoki, Kazunori ; Ohnami, Shumpei ; Yoshida, Kimiko ; Kazui, Teruhisa ; Kato, Nobuyuki ; Inoue, Kazuaki ; Kohara, Michinori ; Yoshida, Teruhiko. / Adenovirus-mediated gene transfer of interferon α inhibits hepatitis C virus replication in hepatocytes. In: Biochemical and Biophysical Research Communications. 2003 ; Vol. 307, No. 4. pp. 814-819.
@article{5e362705b375407bae1ad417782a9173,
title = "Adenovirus-mediated gene transfer of interferon α inhibits hepatitis C virus replication in hepatocytes",
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.",
keywords = "Adenovirus, Gene transfer, Hepatitis C virus, Interferon, Liver cirrhosis",
author = "Koichi Suzuki and Kazunori Aoki and Shumpei Ohnami and Kimiko Yoshida and Teruhisa Kazui and Nobuyuki Kato and Kazuaki Inoue and Michinori Kohara and Teruhiko Yoshida",
year = "2003",
month = "8",
day = "8",
doi = "10.1016/S0006-291X(03)01255-5",
language = "English",
volume = "307",
pages = "814--819",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - Adenovirus-mediated gene transfer of interferon α inhibits hepatitis C virus replication in hepatocytes

AU - Suzuki, Koichi

AU - Aoki, Kazunori

AU - Ohnami, Shumpei

AU - Yoshida, Kimiko

AU - Kazui, Teruhisa

AU - Kato, Nobuyuki

AU - Inoue, Kazuaki

AU - Kohara, Michinori

AU - Yoshida, Teruhiko

PY - 2003/8/8

Y1 - 2003/8/8

N2 - 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.

AB - 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.

KW - Adenovirus

KW - Gene transfer

KW - Hepatitis C virus

KW - Interferon

KW - Liver cirrhosis

UR - http://www.scopus.com/inward/record.url?scp=0038105558&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038105558&partnerID=8YFLogxK

U2 - 10.1016/S0006-291X(03)01255-5

DO - 10.1016/S0006-291X(03)01255-5

M3 - Article

C2 - 12878183

AN - SCOPUS:0038105558

VL - 307

SP - 814

EP - 819

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 4

ER -