2007年1月
Serum-derived hepatitis C virus infectivity in interferon regulatory factor-7-suppressed human primary hepatocytes
JOURNAL OF HEPATOLOGY
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- 巻
- 46
- 号
- 1
- 開始ページ
- 26
- 終了ページ
- 36
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.jhep.2006.08.018
- 出版者・発行元
- ELSEVIER SCIENCE BV
Background/Aims:The development of an efficient in vitro infection system for HCV is important in order to develop new anti-HCV strategy. Only Huh7 hepatocyte cell lines were shown to be infected with JFH-1 fulminant HCV-2a strain and its chimeras. Here we aimed to establish a primary hepatocyte cell line that could be infected by HCV particles from patients' sera.
Methods: We transduced primary human hepatocytes with human telomerase reverse-transcriptase together with human papilloma virus 18/E6E7 (HPV18/E6E7) genes or simian virus large T gene (SV40 T) to immortalize cells. We also established the HPV18/E6E7-immortalized hepatocytes in which interferon regulatory factor-7 was inactivated. Finally we analyzed HCV infectivity in these cells.
Results: Even after prolonged culture HPV18/E6E7-immortalized hepatocytes exhibited hepatocyte functions and marker expression and were more prone to HCV infection than SV40 T-immortalized hepatocytes. The susceptibility of HPV18/E6E7-immortalized hepatocytes to HCV infection was further improved, in particular, by impairing signaling through interferon regulatory factor-7.
Conclusions: HPV18/E6E7-immortalized hepatocytes are useful for the analysis of HCV infection, anti-HCV innate immune response, and screening of antiviral agents with a variety of HCV strains. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Methods: We transduced primary human hepatocytes with human telomerase reverse-transcriptase together with human papilloma virus 18/E6E7 (HPV18/E6E7) genes or simian virus large T gene (SV40 T) to immortalize cells. We also established the HPV18/E6E7-immortalized hepatocytes in which interferon regulatory factor-7 was inactivated. Finally we analyzed HCV infectivity in these cells.
Results: Even after prolonged culture HPV18/E6E7-immortalized hepatocytes exhibited hepatocyte functions and marker expression and were more prone to HCV infection than SV40 T-immortalized hepatocytes. The susceptibility of HPV18/E6E7-immortalized hepatocytes to HCV infection was further improved, in particular, by impairing signaling through interferon regulatory factor-7.
Conclusions: HPV18/E6E7-immortalized hepatocytes are useful for the analysis of HCV infection, anti-HCV innate immune response, and screening of antiviral agents with a variety of HCV strains. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
- リンク情報
- ID情報
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- DOI : 10.1016/j.jhep.2006.08.018
- ISSN : 0168-8278
- PubMed ID : 17112629
- Web of Science ID : WOS:000243350900006