2017 Fiscal Year Annual Research Report
Analysis of regulation mechanisms of hepatitis B virus life cycle by kinases and post-translational modifications
Project/Area Number |
26460565
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Research Institution | National Institute of Infectious Diseases |
Principal Investigator |
渡士 幸一 国立感染症研究所, ウイルス第二部, 主任研究官 (40378948)
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Project Period (FY) |
2014-04-01 – 2018-03-31
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Keywords | HBV |
Outline of Annual Research Achievements |
B型肝炎ウイルス(HBV)複製培養系において、細胞骨格のうち微小管がHBV coreタンパク質と相互作用し、HBV coreタンパク質の多量体化によるキャプシド形成に関わっていることが示された。この制御機構は、微小管形成阻害剤であるノコダゾールやビンブラスチン、コルヒチンを処理することにより阻害され、結果的に細胞内のHBVキャプシド形成量が低下し、ウイルス複製活性が減少することが認められた。この結果は細胞をコンフルエントの状態で得られたものであり、細胞毒性も認められなかったことから、微小管への効果に依存すると考えられた。これまで我々はテトラサイクリンによりHBV複製をon/off可能なHepAD38細胞を親株として、シングルセルクローニング法によってHBV複製活性の高い細胞クローン(Hep38.7-Tet細胞)と低い細胞クローン(Hep38.3-Tet細胞)を得ていたが、後者に比較して前者では微小管タンパク質チューブリンとHBV coreタンパク質の相互作用が強く、またキャプシド形成活性が高いことが明らかとなった。このことより、今回明らかにした機構は実際のHBV複製活性制御に重要であることが示唆された。これは査読付き国際誌に論文として発表した。また一方で、チューブリンの翻訳後修飾がHBV複製活性を制御していることを示唆するデータが得られた。このことから、キナーゼなどを含めた因子と微小管の関連を解析することにより、今後新たなHBV複製機構、また創薬標的が明らかになると期待される。
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Research Products
(68 results)
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[Journal Article] De Novo Macrocyclic Peptide Inhibitors of Hepatitis B Virus Cellular Entry2018
Author(s)
Passioura T, Watashi K, Fukano K, Shimura S, Saso W, Morishita R, Ogasawara Y, Tanaka Y, Mizokami M, Sureau C, Suga H, Wakita T
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Journal Title
Cell Chem Biol
Volume: S2451-9456(18)
Pages: 30125-30129
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Functional association of cellular microtubules with viral capsid assembly supports efficient hepatitis B virus replication2017
Author(s)
Iwamoto M, Cai D, Sugiyama M, Suzuki R, Aizaki H, Ryo A, Ohtani N, Tanaka Y, Mizokami M, Wakita T, Guo H, Watashi K
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Journal Title
Sci Rep
Volume: 7
Pages: 10620
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Chemical array system, a platform to identify novel hepatitis B virus entry inhibitors targeting sodium taurocholate cotransporting polypeptide2017
Author(s)
Kaneko M, Futamura Y, Tsukuda S, Kondoh Y, Sekine T, Hirano H, Fukano K, Ohashi H, Saso W, Morishita R, Matsunaga S, Kawai F, Ryo A, Park SY, Suzuki R, Aizaki H, Ohtani N, Sureau C, Wakita T, Osada H, Watashi K
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Journal Title
Sci Rep
Volume: 8
Pages: 2769
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Acute Hepatitis B in Japan, April 1999 ~ December 20152017
Author(s)
Zheng X, Aoyagi H, Hossam G, Zaitsu T, Puig-Basagoiti F, Kao Y, Watashi K, Suzuki R, Takahashi T, Sunagawa T, Oishi K, Wakita T, Aizaki H
Organizer
5th JAPAN-TAIWAN-KOREA HBV Research Symposium 2017
Int'l Joint Research
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[Presentation] Identification of HBV entry inhibitors without interfering with the NTCP transporter activity2017
Author(s)
Fukano K, Shimura S, Peel M, Sluder A, Kawai F, Tsukuda S, Suzuki R, Aizaki H, Park SY, Wakita T, Ogasawara Y, Watashi K
Organizer
5th JAPAN-TAIWAN-KOREA HBV Research Symposium 2017
Int'l Joint Research
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[Presentation] C型慢性肝炎のウイルス学的著効(SVR)後の肝実質細胞のオルガネラ異常の解析2017
Author(s)
青柳東代, 飯島尋子, Francesc Puig-Basagoiti, Zheng Xin, Yu Ting Kao, Gewaid E. Hossam, 在津拓馬, 松田麻未, 渡士幸一, 鈴木亮介, 政木隆博, 島田紀明, 加藤慶三, 坪田昭人, 三又絢子, 酒巻有里子, 市野瀬志津子, 和氣健二郎, 脇田隆字, 相崎英樹
Organizer
第27回抗ウイルス療法学会学術集会・総会
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[Presentation] 1999年から2015年までの日本におけるB型急性肝炎4273症例の疫学解析2017
Author(s)
Zheng Xin, 青柳東代, Gewaid E. Hossam, 在津拓馬, Puig-Basagoiti Francesc, Yu Ting Kao, 渡士幸一, 鈴木亮介, 高橋琢理, 砂川富正, 大石和徳, 脇田隆字. 相崎英樹
Organizer
第53回日本肝臓学会総会
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[Presentation] Abnormal organelles were continuously observed in sustained virological response (SVR) patients2017
Author(s)
Aoyagi H, Iijima H, Puig-Basagoiti F, Zheng X, Kao YT, Gewaid HE, Zaitsu T, Matsuda M, Watashi K, Suzuki R, Masaki T, Shimada N, Kato K, Tsubota A, Mimata A, Sakamaki Y, Ichinose S, Wake K, Wakita T, Aizaki H
Organizer
The Asian Pacific Associaton for the Study of the Liver - Single Topic Conference 2017
Int'l Joint Research
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[Presentation] Sphingomyelin participates in the formation of Hepatitis C virus membrane replication vesicles2017
Author(s)
Gewaid HE, Aoyagi H, Arita M, Watashi K, Suzuki R, Aly HH, Kumagai K, Yamaji T, Fukasawa M, Mimata A, Sakamaki Y, Ichinose S, Hanada K, Wakita T, Aizaki H
Organizer
American Society for Virology - 2017 Annual Meeting
Int'l Joint Research
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[Presentation] The integrity of cellular microtubule structure is important for an efficient HBV capsid formation2017
Author(s)
Iwamoto M, Cai D, Sugiyama M, Suzuki R, Aizaki H, Ryo A, Ohtani N, Tanaka Y, Mizokami M, Wakita T, Guo H, Watashi K
Organizer
2017 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
Int'l Joint Research
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[Presentation] Membrane protein, embryonic lethal, abnormal vision, drosophila-like 1, interacts with NS5A and involves in hepatitis C virus replication2017
Author(s)
Kao YT, Goto K, Aoyagi H, Hossam GE, Zheng X, Puig-Basagoiti F, Watashi K, Suzuki R, Yamagoe S, Dohmae N, Suzuki T, Okushin K, Tsutsumi T, Yotsuyanagi H, Moriya K, Koike K, Suzuki T, Wakita T, Aizaki H
Organizer
The 65th Annual Meeting of the Japanese Society for Virology
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[Presentation] Interaction of hepatitis B virus core protein with microtubles is important for the efficient capsid formation2017
Author(s)
Iwamoto M, Cai D, Sugiyama M, Suzuki R, Aizaki H, Ryo A, Ohtani N, Tanaka Y, Mizokami M, Wakita T, Watashi K
Organizer
The 65th Annual Meeting of the Japanese Society for Virology
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[Presentation] Generation of hepatitis C virus vaccine antigen based on Japanese encephalitis virus subviral particles2017
Author(s)
Yato K, Matsuda M, Watanabe N, Nakajima S, Fujimoto A, Watashi K, Aizaki H, Kato T, Tamura K, Wakita T, Suzuki R
Organizer
The 65th Annual Meeting of the Japanese Society for Virology
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[Presentation] Crosstalk of Xenobiotic Metabolism Pathway with Lipid Metabolism regulates the Host Permissiveness to Hepatitis C Virus Production2017
Author(s)
Ohashi H, Nakajima S, Kim S, Suzuki R, Aizaki H, Fukasawa M, Kamisuki S, Sugawara F, Ohtani N, Wakita T, Watashi K
Organizer
第14回ウイルス学キャンプin湯河原
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[Presentation] Antiviral effect of bile acid derivatives on hepatitis B virus infection2017
Author(s)
Okumura A, Ito K, Watashi K, Takeuchi J, Inoue R, Suzuki S, Sakamoto K, Okutsu S, Umezawa K, Wakita T, Yoneda M
Organizer
2017 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
Int'l Joint Research
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[Presentation] An Epidemiology Study of Acute Hepatitis B in Japan, April 1999 ~ December 20152017
Author(s)
Zheng X, Aoyagi H, Hossam G, Zaitsu T, Puig-Basagoiti F, Kao Y, Watashi K, Suzuki R, Takahashi T, Sunagawa T, Oishi K, Wakita T, Aizaki H
Organizer
2017 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
Int'l Joint Research
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[Presentation] NS5A-Associated Membrane Protein, Embryonic Lethal, Abnormal Vision, Drosophila-Like 1, Involves in Hepatitis C Replication2017
Author(s)
Kao YT, Goto K, Aoyagi H, Hossam GE, Zheng X, Puig-Basagoiti F, Watashi K, Suzuki R, Yamagoe S, Dohmae N, Suzuki T, Okushin K, Tsutsumi T, Yotsuyanagi H, Moriya K, Koike K, Suzuki T, Wakita T, Aizaki H
Organizer
24th International Symposium on Hepatitis C Virus and Related Viruses
Int'l Joint Research
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[Presentation] Novel Crosstalk of Xenobiotic Response with Lipid Metabolism Regulates the Host Permissiveness to Hepatitis C Virus Production2017
Author(s)
Ohashi H, Nakajima S, Kim S, Suzuki R, Aizaki H, Fukasawa M, Kamisuki S, Sugawara F, Ohtani N, Wakita T, Watashi K
Organizer
24th International Symposium on Hepatitis C Virus and Related Viruses
Int'l Joint Research
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[Presentation] Human hepatic stellate cells are permissive for hepatitis C virus infection/replication and play important roles in fibrosis2017
Author(s)
Zheng X, Zaitsu T, Aoyagi H, Matsuda M, Watanabe N, Fujimoto A, Watashi K, Suzuki R, Fukuhara T, Matsuura Y, Ichinose S, Wake K, Suzuki T, Iijima H, Yokoyama H, Masaki T, Matsuura T, Tamura K, Wakita T, Aizaki H
Organizer
The 65th Annual Meeting of the Japanese Society for Virology
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[Presentation] Abnormal hepatocellular organelles remain to be observed in sustained virological response patients2017
Author(s)
Aoyagi H, Iijima H, Puig-Basagoiti F, Zheng X, Kao YT, Hossam GE, Matsuda M, Watashi K, Suzuki R, Masaki T, Aizawa N, Shimada N, Kato K, Tsubota A, Mimata A, Sakamaki Y, Ichinose S, Wake K, Wakita T, Aizaki H
Organizer
The 65th Annual Meeting of the Japanese Society for Virology
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