Negative regulation of intracellular hepatitis C virus replication by interferon regulatory factor 3
| Autor: | Yoko Tanabe, Mamoru Watanabe, Tsuyoshi Yamashiro, Naoya Sakamoto, Yasuhiro Itsui, Nobuhiko Kanazawa, Yoshie Takeda, Mina Nakagawa, Nobuyuki Enomoto, Shinya Maekawa, Hiroshi Sakugawa, Masayuki Kurosaki, Tomoyuki Koyama, Cheng-Hsin Chen |
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| Rok vydání: | 2006 |
| Předmět: |
Gene Expression Regulation
Viral Hepatitis C virus Blotting Western Gene Expression Hepacivirus Biology Transfection Virus Replication medicine.disease_cause Plasmid Cell Line Tumor medicine Humans Replicon RNA Small Interfering Regulation of gene expression Gastroenterology Immunohistochemistry Virology IRF1 Interferon Regulatory Factor-3 IRF8 Intracellular Plasmids Interferon regulatory factors |
| Zdroj: | Journal of Gastroenterology. 41:750-757 |
| ISSN: | 1435-5922 0944-1174 |
| Popis: | Interferon regulatory factor (IRF)-3 plays an important role in initiating cellular interferon-stimulated gene-mediated antiviral responses. In the present study, we evaluated the effects of IRF-3 expression and activation on intracellular hepatitis C virus (HCV) replication using an HCV replicon system.An HCV replicon was constructed that expressed a neomycin-selectable chimeric firefly luciferase reporter protein. A small interfering (si) RNA oligonucleotide directed against IRF-3 mRNA was designed and synthesized. A eukaryote expression plasmid vector was constructed that expressed IRF-3 mRNA under control of the cytomegalovirus early promoter/enhancer. To evaluate transcriptional activity of the interferon-stimulated genes, a reporter vector was used that expressed firefly luciferase under control of the interferon-stimulated response element (ISRE).The baseline expression of IRF-3 did not significantly differ between cells with and without expression of the replicon. Transfection of an IRF-3 expression plasmid into the cells raised the ISRE-luciferase activities. The increase of ISRE activity was significantly more potent in the replicon-expressing cells than in cells without replicon expression. Concomitantly, the overexpression of IRF-3 suppressed HCV replication levels. In contrast, siRNA knockdown of IRF-3 suppressed ISRE activity by 38% +/- 2%. Interestingly, the suppression of IRF-3 resulted in a significant increase of HCV replication, by up to twofold, depending on the IRF-3 suppression levels.IRF-3 negatively regulated intracellular HCV replication, and was partially activated in cells that expressed the HCV replicon. Thus, IRF-3 is a key molecule controlling HCV replication through modulation of host interferon gene responses. |
| Databáze: | OpenAIRE |
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