Tissue macrophages are responsible for inflammatory liver disease in the hepatitis C virus transgenic mice
Project/Area Number |
24390117
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Virology
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Research Institution | Tokyo Metropolitan Institute of Medical Science |
Principal Investigator |
KOHARA Michinori 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, プロジェクトリーダー (10250218)
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Co-Investigator(Kenkyū-buntansha) |
HIRATA Yuichi 公益財団財団法人東京都医学総合研究所, ゲノム医科学研究分野, 研究員 (50439452)
YASUI Fumihiko 公益財団財団法人東京都医学総合研究所, ゲノム医科学研究分野, 主席研究員 (40399473)
MUNAKATA Tsubasa 公益財団財団法人東京都医学総合研究所, ゲノム医科学研究分野, 主席研究員 (50420237)
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Project Period (FY) |
2012-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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Keywords | C型肝炎ウイルス / 持続感染化 / 宿主免疫応答 / ウイルス排除 / 免疫学 / C型肝炎ウイルス / 脂肪変性 |
Outline of Final Research Achievements |
We have reported that hepatitis C virus transgenic mice (HCV Tg) caused continuous liver injury and developed hepatocellular carcinoma through the Cre/loxP switching system. In addition, we showed recombinant vaccinia viruses expressing HCV nonstructural protein (rVV-N25) could protect against the progression of chronic hepatitis by way of suppression of macrophages activation. We focused on the role of tissue macrophages for liver disease of the HCV Tg mice and examined characteristic features of macrophages following rVV-N25 treatment. rVV-N25 treatment suppressed cell number and cytokine production on macrophages in the liver. M2 macrophages contribute to the induction of chronic liver inflammation in HCV mouse models. In addition, rVV-N25 induced therapeutic effect on liver tissue due to suppressed macrophage recruitment and activation.
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Report
(5 results)
Research Products
(75 results)
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[Journal Article] The RNA Sensor RIG-I Dually Functions as an Innate Sensor and Direct Antiviral Factor for Hepatitis B Virus2015
Author(s)
Sato S, Li K, Kameyama T, Hayashi T, Ishida Y, Murakami S, Watanabe T, Iijima S, Sakurai Y, Watashi K, Tsutsumi S, Sato Y, Akita H, Wakita T, Rice CM, Harashima H, Kohara M, Tanaka Y, Takaoka A
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Journal Title
Immunity
Volume: 42
Issue: 1
Pages: 123-132
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] In vivo therapeutic potential of Dicer-hunting siRNAs targeting infectious hepatitis C virus2014
Author(s)
Watanabe T, Hatakeyama H, Matsuda-Yasui C, Sato Y, Sudoh M, Takagi A, Hirata Y, Ohtsuki T, Arai M, Inoue K, Harashima H, Kohara M
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Journal Title
Scientific Reports
Volume: in press
Issue: 1
Pages: 4750-4750
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Targeted induction of interferon-λ in humanized chimeric mouse liver abrogates hepatotropic virus infection2013
Author(s)
Nakagawa S, Hirata Y, Kameyama T, Tokunaga Y, Nishito Y, Hirabayashi K, Yano J, Ochiya T, Tateno C, Tanaka Y, Mizokami M, Tsukiyama-Kohara K, Inoue K, Yoshiba M, Takaoka A, Kohara M
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Journal Title
PLoS One
Volume: 8
Issue: 3
Pages: e59611-e59611
DOI
Related Report
Peer Reviewed
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[Journal Article] A serine palmitoyltransferase inhibitor blocks hepatitis C virus replication in human hepatocytes.2013
Author(s)
Katsume A, Tokunaga Y, Hirata Y, Munakata T, Saito M, Hayashi H, Okamoto K, Ohmori Y, Kusanagi I, Fujiwara S, Tsukuda T, Aoki Y, Klumpp K, Tsukivama-Kohara K, El-Gohary A, Sudoh M, Kohara M.
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Journal Title
Gastroenterology
Volume: 145(4)
Issue: 4
Pages: 865-79
DOI
Related Report
Peer Reviewed
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[Journal Article] Hepatitis C virus kinetics by administration of pegylated interferon-lin human and chimeric mice carrying human hepatocytes with variants of the IL28B gene2012
Author(s)
Watanabe T, Sugauchi F, Tanaka Y, Matsuura K, Yatsuhashi H, Murakami S, Iijima S, Iio E, Sugiyama M, Shimada T, Kakuni M, Kohara M, Mizokami M
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Journal Title
Gut
Volume: Nov 7
Issue: 9
Pages: 1340-6
DOI
Related Report
Peer Reviewed
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[Journal Article] HSC90 is required for nascent hepatitis C virus core protein stability in yeast cells.2012
Author(s)
Kubota N, Inayoshi Y, Satoh N. Fukuda T, Iwai K, Tomoda H, Kohara M, Kataoka K, Shimamoto A, Furuichi Y, Nomoto A, Naganuma A, Kuge S
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Journal Title
FEBS Letters
Volume: (in press)
Issue: 16
Pages: 2318-2325
DOI
Related Report
Peer Reviewed
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[Journal Article] Immunization with a recombinant vaccinia virus that encodes nonstructural proteins of the hepatitis C virus suppresses viral protein levels in mouse liver.2012
Author(s)
Sekiguchi, S, Kimura K, Chiyo T, Ohtsuki T, Tobita Y, Tokunaga Y, Yasui F, Tsukiyama-Kohara K, Wakita T, Tanaka T, Miyasaka M, Mizuno K, Hayashi Y, Hishima T, Matsushima K and Kohara M.
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Journal Title
PLoS One
Volume: 7
Issue: 12
Pages: e51656-e51656
DOI
Related Report
Peer Reviewed
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[Presentation] Exosomes contain HBV DNA and HBs Ag2015
Author(s)
Takahiro Sanada, Yuichi Hirata, Yutaka Naito, Naoki Yamamoto, Yuji Ishida, Chihiro Yamasaki, Chise Tateno, Takahiro Ochiya, michinori Kohara
Organizer
2015International Meeting on Molecular Biology of Hepatitis B Viruses
Place of Presentation
Dolce Bad Nauheim (Germany)
Year and Date
2015-10-04
Related Report
Int'l Joint Research
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