Regulation of Hepatitis C Virus Replication by Interferon Regulatory Factor 1

• Nobuhiko Kanazawa

  Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University

• Masayuki Kurosaki

  Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University

• Naoya Sakamoto

  Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University

• Nobuyuki Enomoto

  Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University

• Yasuhiro Itsui

  Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University

• Tsuyoshi Yamashiro

  Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University

• Yoko Tanabe

  Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University

• Shinya Maekawa

  Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University

• Mina Nakagawa

  Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University

• Cheng-Hsin Chen

  Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University

• Sei Kakinuma

  Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University

• Shigeru Oshima

  Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University

• Tetsuya Nakamura

  Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University

• Takanobu Kato

  Department of Microbiology, Tokyo Metropolitan Institute for Neuroscience, Tokyo

• Takaji Wakita

  Department of Microbiology, Tokyo Metropolitan Institute for Neuroscience, Tokyo

• Mamoru Watanabe

  Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University

抄録

Cellular antiviral responses are mediated partly by the expression of interferon-stimulated genes, triggered by viral genomes, their transcripts and replicative intermediates. Persistent replication of a hepatitis C virus (HCV) replicon suggests that the replicon does not elicit cellular innate antiviral responses. In the present study, we investigated regulatory factors of the interferon-mediated antiviral system in cells expressing an HCV replicon. Luciferase reporter assays revealed that the baseline activity of the interferon-stimulated response element (ISRE) was significantly lower in cells harboring the replicon than in naive cells. Among the proteins involved in the IFN/Jak/STAT pathway and in ISRE activity, the expression level of interferon regulatory factor 1 (IRF-1) was found to be significantly lower in cells harboring the replicon. Transfection of an IRF-1 expression construct into cells harboring the replicon caused an increase of ISRE activity, accompanied by suppression of expression of the HCV replicon. Moreover, in cured Huh7 cells from which the HCV replicon had been eliminated, the expression levels of IRF-1 and ISRE activity also were suppressed, demonstrating that the decrease of IRF-1 is attributable, not to active suppression by the viral proteins, but to adaptation of cells that enables replication of the HCV subgenome. The high permissiveness of the cured cells for the replicon was abolished by transgenic supplementation of IRF-1 expression. Taken together, IRF-1 is one of the key host factors that regulate intracellular HCV replication through modulation of interferon-stimulated-gene-mediated antiviral responses.

収録刊行物

• Journal of Virology

  Journal of Virology 78 (18), 9713-9720, 2004-09-15

  American Society for Microbiology

キーワード

• Virology
• Insect Science
• Immunology
• Microbiology

詳細情報

• CRID: 1363670319745996544
• NII論文ID: 30020800413
• DOI: 10.1128/jvi.78.18.9713-9720.2004
• ISSN: 10985514
• ISSN: 0022538X
• Web Site: https://journals.asm.org/doi/pdf/10.1128/JVI.78.18.9713-9720.2004
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