Association analysis between the suppression of interferon responsiveness by HBV infection and changes of gene expression in human hepatocytes
| Project/Area Number |
17KK0194
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| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Hiroshima University |
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Principal Investigator |
Tsuge Masataka 広島大学, 自然科学研究支援開発センター, 助教 (50448263)
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| Project Period (FY) |
2018 – 2019
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
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| Keywords | B型肝炎ウイルス / ウイルス動態 / ヒト肝細胞キメラマウス / 遺伝子発現解析 / ヒト肝細胞 / キメラマウス / インターフェロン |
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| Outline of Final Research Achievements |
Human hepatocyte chimeric mice were infected with hepatitis B virus and thier liver tissues were collected after sacrifice. Total RNA was extracted from the mouse livers and transcribed into cDNA. Then gene expression analyses were perfomred using these cDNA and gene expression profiles were compared between HBV-infected and non-infected mice. Resulting these analyses, we identified that similar viral kinetic pattern could be observed regardless to HBV clones and that pathways associated with immune responses, cell growth or apoptosis were significantly activated in human hepatocytes after HBV infection. Furthermore, we also identified that intracellular resposes by HBV infection were different among HBV genotypes.
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| Academic Significance and Societal Importance of the Research Achievements |
年間50万人以上がB型肝炎ウイルス感染により死亡するとされ、特にアジア地域ではその感染者数が多い。そのため、B型慢性肝炎に対する治療薬の開発は急務であり、現在、治療薬開発に向けた研究が進められ、新規治療薬の登場が期待されている。このような背景から、治療薬開発において、抗ウイルス効果が評価可能な動物モデルの作製は非常に重要であり、また本研究のようなウイルス動態の視点から評価も必須と言える。本研究を進めていくことで、B型肝炎治療に向けた治療標的が同定され、本研究で得られた遺伝子発現プロファイルが新規治療薬開発の基盤として活用できる可能性がある。
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Report
(3 results)
Research Products
(12 results)
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[Journal Article] Early Multiphasic HBV Infection Initiation Kinetics Is Not Clone-Specific and Is Not Affected by Hepatitis D Virus (HDV) Infection2019
Author(s)
Tsuge Masataka, Uchida Takuro, Walsh Kevin, Ishida Yuji, Tateno Chise, Kumar Upendra, Glenn Jeffrey, Koh Christopher, Heller Theo, Uprichard Susan, Dahari Harel, Chayama Kazuaki
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Journal Title
Viruses
Volume: 11
Issue: 3
Pages: 263-263
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Comparison of intracellular responses between HBV genotype A and C infection in human hepatocyte chimeric mice2019
Author(s)
Tsushima K, Tsuge M, Hiraga N, Uchida T, Murakami E, Makokha GN, Kurihara M, Nomura Motonobu, Hiyama Y, Fujino H, Ono A, Nakahara T, Yamauchi M, Abe-Chayama H, Kawaoka T, Miki D, Imamura M, Aikata H, Hayes CN, Chayama K
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Journal Title
Journal of Gastroenterology
Volume: 印刷中
Issue: 7
Pages: 650-659
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Investigation of infectivity of serum-derived HBV from patients and human hepatocyte chimeric mouse to HepG2/NTCP cells.2019
Author(s)
Hatsue Fujino, Miko Namba, Atsushi Ono, Takashi Nakahara, Eisuke Murakami, Masami Yamauchi, Tomokazu Kawaoka, Daiki Miki, Masataka Tsuge, Hiromi Abe-Chayama, C. Hayes Nelson, Michio Imamura, Hiroshi Aikata, Kazuaki Chayama
Organizer
International HBV meeting 2019
Related Report
Int'l Joint Research
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[Presentation] Serum atutotaxin levels is useful to evaluate fibrosis during entecavir therapy and to predict the development of hepatocellular carcinoma in patients with chronic hepatitis B.2019
Author(s)
Hatsue Fujino, Kei Morio, Atsushi Ono, Takashi Nakahara, Eisuke Murakami, Masami Yamauchi, Tomokazu Kawaoka, Daiki Miki, Masataka Tsuge, Hiromi Abe-Chayama, C. Hayes Nelson, Michio Imamura, Hiroshi Aikata, Kazuaki Chayama
Organizer
International HBV meeting 2019
Related Report
Int'l Joint Research
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