新規培養系を利用したB型肝炎ウイルス侵入機序・宿主因子の包括的解析

2018 Fiscal Year Annual Research Report

• Project/Area Number: 17H04085
• 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)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: HBV / NTCP / EGFR

Outline of Annual Research Achievements

B型肝炎ウイルス(HBV)の宿主細胞への感染を理解するためには、いまだほとんどその機序が明らかでない感染初期のウイルス細胞内侵入過程を解析する必要がある。これまでHBVの宿主細胞への感染には細胞側受容体としてNTCPが必要であることが明らかになっている一方で、NTCPがどのようにHBV侵入を媒介するか、これを介した細胞内での動態に関してはほとんど不明である。またHBVの種特異的な感染を決定する機構も完全には明らかになっていない。本研究ではNTCPと相互作用あるいは制御する因子を同定することによりHBV侵入機構を明らかにすることを目的とした。特にこれまでに我々が樹立したHBV感染培養系を用いてHBV感染表現系を指標に、これに関わる宿主因子を同定することを主な目的に設定した。本年度は同定した候補因子の中から、NTCPを制御する因子として上皮成長因子受容体(EGFR)に着目し、その機能およびHBV感染への意義を解析し、報告した(Iwamoto M et al. Proc Natl Acad Sci USA 116(17): 8487-8492, 2019)。EGFRとNTCPの相互作用はウイルス受容体機能に重要であり、特にウイルスの細胞への吸着後の内在化過程に関与すると考えられた。本研究成果は、HBV分子機構の解明のみならず、HBV侵入動態、種特異的感染、創薬にも有用な知見を提供するものである。

Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

これまで宿主細胞へのHBV侵入には受容体NTCPが必須であることが知られていたが、NTCPはどのようにHBV侵入を媒介するかは明らかでなかった。本研究ではEGFRがNTCPと相互作用し、NTCPの受容体機能に必要な受容体共役因子であることを明らかにした。HBV preS1はNTCPだけでなくEGFRと共に内在化することが示された。EGFRと相互作用できないNTCP点変異体はHBV侵入、感染を媒介することができなかった。またEGFR-NTCP相互作用を解離させるペプチドを処理することによりNTCP-HBV preS1複合体の内在化は抑制され、HBV感染は阻害された。EGFR阻害剤ゲフィチニブの処理によってもEGFR-NTCP-HBV preS1の内在化が抑制され、HBV感染が大きく低下した。以上の結果はNTCPのウイルス受容体機能にはEGFRとの機能的相互作用が重要であることを示している。これは、これまで明らかでなかったNTCPのウイルス受容体媒介メカニズムを理解する上で重要な情報である。

Strategy for Future Research Activity

本研究によりEGFRのHBV感染における役割が明らかになった。今後EGFRがどのようにNTCP受容体機能を制御しているのかを明らかにしていく。またEGFRとNTCPの機能的相互作用が新たな抗HBV薬の標的となると考えられるので、EGFR-NTCP相互作用をin vitroで評価するスクリーニング系を構築することでHBV感染阻害薬を同定できると考えられる。

Research Products

• [Int'l Joint Research] INTS(フランス)
  • Country Name: FRANCE
  • Counterpart Institution: INTS
• [Int'l Joint Research] Pennsylvania State University(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: Pennsylvania State University
• [Int'l Joint Research] National Taiwan University(台湾)
  • Country Name: 台湾
  • Counterpart Institution: National Taiwan University
• [Journal Article] Epidermal growth factor receptor is a host-entry cofactor triggering hepatitis B virus internalization (2019)
  • Author(s): Iwamoto M, Saso W, Sugiyama R, Ishii K, Ohki M, Nagamori S, Suzuki R, Aizaki H, Ryo A, Yun JH, Park SY, Ohtani N, Muramatsu M, Iwami S, Tanaka Y, Sureau C, Wakita T, Watashi K
  • Journal Title: Proc Natl Acad Sci USA Volume: 116 Pages: 8487-8492
  • DOI: 10.1073/pnas.1811064116
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Concept of Viral Inhibitors via NTCP (2019)
  • Author(s): Fukano K, Tsukuda S, Watashi K, Wakita T
  • Journal Title: Semin Liver Dis Volume: 39 Pages: 78-85
  • DOI: 10.1055/s-0038-1676804
  • Peer Reviewed
• [Journal Article] Screening for inhibitor of episomal DNA identified dicumarol as a hepatitis B virus inhibitor (2019)
  • Author(s): Takeuchi F, Ikeda S, Tsukamoto Y, Iwasawa Y, Qihao C, Otakaki Y, Ryota O, Yao WL, Narita R, Makoto H, Watashi K, Wakita T, Takeuchi K, Chayama K, Kogure A, Kato H, Fujita T
  • Journal Title: PLoS One Volume: 14 Pages: e0212233
  • DOI: 10.1371/journal.pone.0212233
  • Peer Reviewed / Open Access
• [Journal Article] Activation of protein kinase R by hepatitis C virus RNA-dependent RNA polymerase (2019)
  • Author(s): Suzuki R, Matsuda M, Shimoike T, Watashi K, Aizaki H, Kato T, Suzuki T, Muramatsu M, Wakita T
  • Journal Title: Virology Volume: 529 Pages: 226-233
  • DOI: 10.1016/j.virol.2019.01.024
  • Peer Reviewed
• [Journal Article] Troglitazone Impedes the Oligomerization of Sodium Taurocholate Cotransporting Polypeptide and Entry of Hepatitis B Virus Into Hepatocytes (2019)
  • Author(s): Fukano K, Tsukuda S, Oshima M, Suzuki R, Aizaki H, Ohki M, Park SY, Muramatsu M, Wakita T, Sureau C, Ogasawara Y, Watashi K
  • Journal Title: Front Microbiol Volume: 9 Pages: 3257
  • DOI: 10.3389/fmicb.2018.03257
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mathematical Analysis of a Transformed ODE from a PDE Multiscale Model of Hepatitis C Virus Infection (2019)
  • Author(s): Kitagawa K, Kuniya T, Nakaoka S, Asai Y, Watashi K, Iwami S
  • Journal Title: Bull Math Biol Volume: 81 Pages: 1427-1441
  • DOI: 10.1007/s11538-018-00564-y
  • Peer Reviewed
• [Journal Article] Peroxiredoxin 1, a Novel HBx-Interacting Protein, Interacts with Exosome Component 5 and Negatively Regulates Hepatitis B Virus (HBV) Propagation through Degradation of HBV RNA (2019)
  • Author(s): Deng L, Gan X, Ito M, Chen M, Aly HH, Matsui C, Abe T, Watashi K, Wakita T, Suzuki T, Okamoto T, Matsuura Y, Mizokami M, Shoji I, Hotta H
  • Journal Title: J Virol Volume: 93 Pages: pii: e02203-18
  • DOI: 10.1128/JVI.02203-18
  • Peer Reviewed
• [Journal Article] A Single Adaptive Mutation in Sodium Taurocholate Cotransporting Polypeptide Induced by Hepadnaviruses Determines Virus Species Specificity (2019)
  • Author(s): Takeuchi JS, Fukano K, Iwamoto M, Tsukuda S, Suzuki R, Aizaki H, Muramatsu M, Wakita T, Sureau C, Watashi K
  • Journal Title: J Virol Volume: 93 Pages: pii: e01432-18
  • DOI: 10.1128/JVI.01432-18
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Acidic polysaccharides isolated from marine algae inhibit the early step of viral infection (2019)
  • Author(s): Ueno M, Nogawa M, Siddiqui R, Watashi K, Wakita T, Kato N, Ikeda M, Okimura T, Isaka S, Oda T, Ariumi Y
  • Journal Title: Int J Biol Macromol Volume: 124 Pages: 282-290
  • DOI: 10.1016/j.ijbiomac.2018.11.152
  • Peer Reviewed
• [Journal Article] B型肝炎ウイルス培養系構築から創薬研究へ (2019)
  • Author(s): 深野顕人、渡士幸一
  • Journal Title: 薬学雑誌 Volume: 139 Pages: 81-87
  • DOI: 10.1248/yakushi.18-00164-4
  • Peer Reviewed / Open Access
• [Journal Article] High-throughput neutralization assay for multiple flaviviruses based on single-round infectious particles using dengue virus type 1 reporter replicon (2018)
  • Author(s): Matsuda M, Yamanaka A, Yato K, Yoshii K, Watashi K, Aizaki H, Konishi E, Takasaki T, Kato T, Muramatsu M, Wakita T, Suzuki R
  • Journal Title: Sci Rep Volume: 8 Pages: 16624
  • DOI: 10.1038/s41598-018-34865-y
  • Peer Reviewed / Open Access
• [Journal Article] The aryl hydrocarbon receptor-cytochrome P450 1A1 pathway controls lipid accumulation and enhances the permissiveness for hepatitis C virus assembly (2018)
  • Author(s): Ohashi H, Nishioka K, Nakajima S, Kim S, Suzuki R, Aizaki H, Fukasawa M, Kamisuki S, Sugawara F, Ohtani N, Muramatsu M, Wakita T, Watashi K
  • Journal Title: J Biol Chem Volume: 293 Pages: 19559-19571
  • DOI: 10.1074/jbc.RA118.005033
  • Peer Reviewed
• [Journal Article] Cell and Animal Models for Studying Hepatitis B Virus Infection and Drug Development (2018)
  • Author(s): Hu J, Lin YY, Chen PJ, Watashi K, Wakita T
  • Journal Title: Gastroenterology Volume: 156 Pages: 338-354
  • DOI: 10.1053/j.gastro.2018.06.093
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] IL-1β/ATF3-mediated induction of Ski2 expression enhances hepatitis B virus x mRNA degradation (2018)
  • Author(s): Shiromoto F, Aly HH, Kudo H, Watashi K, Murayama A, Watanabe N, Zheng X, Kato T, Chayama K, Muramatsu M, Wakita T
  • Journal Title: Biochem Biophys Res Commun Volume: 503 Pages: 1854-1860
  • DOI: 10.1016/j.bbrc.2018.07.126
  • Peer Reviewed
• [Journal Article] Screening of microRNAs for a repressor of hepatitis B virus replication (2018)
  • Author(s): Naito Y, Hamada-Tsutsumi S, Yamamoto Y, Kogure A, Yoshioka Y, Watashi K, Ochiya T, Tanaka Y
  • Journal Title: Oncotarget Volume: 9 Pages: 29857-29868
  • DOI: 10.18632/oncotarget.25557
  • Peer Reviewed / Open Access
• [Journal Article] Flap endonuclease 1 is involved in cccDNA formation in the hepatitis B virus (2018)
  • Author(s): Kitamura K, Que L, Shimadu M, Koura M, Ishihara Y, Wakae K, Nakamura T, Watashi K, Wakita T, Muramatsu M
  • Journal Title: PLoS Pathog Volume: 14 Pages: e1007124
  • DOI: 10.1371/journal.ppat.1007124
  • Peer Reviewed / Open Access
• [Journal Article] Development of a cell-based assay to identify hepatitis B virus entry inhibitors targeting the sodium taurocholate cotransporting polypeptide (2018)
  • Author(s): Miyakawa K, Matsunaga S, Yamaoka Y, Dairaku M, Fukano K, Kimura H, Chimuro T, Nishitsuji H, Watashi K, Shimotohno K, Wakita T, Ryo A
  • Journal Title: Oncotarget Volume: 9 Pages: 23681-23694
  • DOI: 10.18632/oncotarget.25348
  • Peer Reviewed / Open Access
• [Journal Article] Rosmarinic acid is a novel inhibitor for Hepatitis B virus replication targeting viral epsilon RNA-polymerase interaction (2018)
  • Author(s): Tsukamoto Y, Ikeda S, Uwai K, Taguchi R, Chayama K, Sakaguchi T, Narita R, Yao WL, Takeuchi F, Otakaki Y, Watashi K, Wakita T, Kato H, Fujita T
  • Journal Title: PLoS One Volume: 13 Pages: e0197664
  • DOI: 10.1371/journal.pone.0197664
  • Peer Reviewed / Open Access
• [Journal Article] De Novo Macrocyclic Peptide Inhibitors of Hepatitis B Virus Cellular Entry (2018)
  • 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
  • Journal Title: Cell Chem Biol Volume: 25 Pages: 906-915
  • DOI: 10.1016/j.chembiol.2018.04.011
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A new strategy to identify hepatitis B virus entry inhibitors by AlphaScreen technology targeting the envelope-receptor interaction (2018)
  • Author(s): Saso W, Tsukuda S, Ohashi H, Fukano K, Morishita R, Matsunaga S, Ohki M, Ryo A, Park SY, Suzuki R, Aizaki H, Muramatsu M, Sureau C, Wakita T, Matano T, Watashi K
  • Journal Title: Biochem Biophys Res Commun Volume: 501 Pages: 374-379
  • DOI: 10.1016/j.bbrc.2018.04.187
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Inhibitory effect of fasiglifam on hepatitis B virus infections through suppression of the sodium taurocholate cotransporting polypeptide (2018)
  • Author(s): Nio Y, Akahori Y, Okamura H, Watashi K, Wakita T, Hijikata M
  • Journal Title: Biochem Biophys Res Commun Volume: 501 Pages: 820-825
  • DOI: 10.1016/j.bbrc.2018.04.199
  • Peer Reviewed
• [Journal Article] A PDE multiscale model of hepatitis C virus infection can be transformed to a system of ODEs (2018)
  • Author(s): Kitagawa K, Nakaoka S, Asai Y, Watashi K, Iwami S
  • Journal Title: J Theor Biol Volume: 448 Pages: 80-85
  • DOI: 10.1016/j.jtbi.2018.04.006
  • Peer Reviewed
• [Presentation] B型肝炎ウイルス培養系と 薬剤開発への応用 (2019)
  • Author(s): 渡士 幸一
  • Organizer: 京都大学ウイルス・再生医科学研究所 再生医学・再生医療の先端融合的共同研究拠点 ウイルス感染症・生命科学先端融合的共同研究拠点 平成30年度共同研究合同報告会
  • Invited
• [Presentation] NTCP/SLC10A1 の胆汁酸取り込み機能に影響しない選択的B型肝炎ウイルス侵入阻害ペプチドの同定 (2019)
  • Author(s): 深野 顕人, Toby PASSIOURA, 志村 聡美, 佐宗 若奈, 森下 了, 小笠原 裕樹, 田中 靖人, 溝上 雅史, Camille SUREAU, 脇田 隆字, 菅 裕明, 渡士 幸一
  • Organizer: 日本薬学会第139年会
• [Presentation] Interaction of host and hepatitis viruses as a target for drug development (2018)
  • Author(s): Koichi Watashi
  • Organizer: Taiwan Society of Virology, Symposium in Memory of Dr. Kuan-Teh Jeang: Human Retrovirus and Hepatitis virus
  • Int'l Joint Research / Invited
• [Presentation] Clinical and Virological Significance of NTCP Receptor in HBV (2018)
  • Author(s): Koichi Watashi
  • Organizer: 2018 APASL Single Topic Conference on Hepatitis B Virus (2018 APASL STC Taipei)
  • Int'l Joint Research / Invited
• [Presentation] Cell entry inhibition as an antiviral strategy (2018)
  • Author(s): Koichi Watashi
  • Organizer: 2018 APASL Single Topic Conference on Hepatitis B Virus (2018 APASL STC Taipei)
  • Int'l Joint Research / Invited
• [Presentation] 核内受容体を利用した肝炎ウイルス増殖戦略 (2018)
  • Author(s): 渡士 幸一
  • Organizer: 日本大学医学部セミナー
  • Invited
• [Presentation] HBVエントリー阻害剤Tomatineの同定と抗HBV活性の解析 (2018)
  • Author(s): 古谷裕, 戸口真理子, 佐藤裕美, 九十田千子, 渡士幸一, 湯川博, 石川哲也, 黒田俊一, 上田啓次, 田中靖人, 脇田隆字, 小嶋聡一
  • Organizer: 第28回抗ウイルス療法学会学術集会・総会
• [Presentation] スフィンゴ脂質のC型肝炎ウイルス複製における役割の解析 (2018)
  • Author(s): 相崎英樹, ホッサムゲワイド, 青柳東代, Zheng Xin, Fransec Puig-Basagoiti, 渡士幸一, 鈴木亮介, 熊谷圭悟, 山地俊之, 深澤征義, 酒巻有里子, 花田賢太郎, 村松正道, 脇田隆字
  • Organizer: 第28回抗ウイルス療法学会学術集会・総会
• [Presentation] 培養細胞系を利用した HBV cccDNA ダイナミクスの定量的検討 (2018)
  • Author(s): 渡士 幸一, 九十田 千子, 脇田 隆字
  • Organizer: 第54回日本肝臓学会総会
• [Presentation] B型肝炎ウイルスの創薬研究 (2018)
  • Author(s): 脇田 隆字, 渡士 幸一
  • Organizer: 第54回日本肝臓学会総会
• [Presentation] Aryl hydrocarbon receptor-cytochrome p450 1a1 pathway regulates hepatic lipid biosynthesis to maximize Hepatitis C virus production (2018)
  • Author(s): Ohashi H, Nakajima S, Kim S, Suzuki R, Aizaki H, Fukasawa M, Kamisuki S, Sugawara F, Ohtani N, Muramatsu M, Wakita T, Watashi K
  • Organizer: 25th International Symposium on Hepatitis C Virus and Related Viruses
  • Int'l Joint Research
• [Presentation] Hepatitis C virus infection triggers the transactivation of aryl hydrocarbon receptor to rearrange hepatic lipid biosynthesis (2018)
  • Author(s): Ohashi H, Nakajima S, Kim S, Suzuki R, Aizaki H, Fukasawa M, Kamisuki S, Sugawara F, Ohtani N, Muramatsu M, Wakita T, Watashi K
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Oligomerization of NTCP is required for hepatitis B virus internalization (2018)
  • Author(s): Fukano K, Tsukuda S, Ohki M, Park S, Suzuki R, Aizaki H, Muramatsu M, Wakita T, Ogasawara Y, Watashi K
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] AlphaScreen technology targeting the viral envelope-receptor interaction identified a novel HBV entry inhibitor, rapamycin (2018)
  • Author(s): Saso W, Tsukuda S, Ohashi H, Fukano K, Morishita R, Matsunaga S, Ohki M, Ryo A, Park S, Suzuki R, Aizaki H, Muramatsu M, Wakita T, Matano T, Watashi K
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Generation of monocloneal antibodies against hepatitis B virus preS1 region from antigen-specific memory B cells (2018)
  • Author(s): Yato K, Onodera T, Matsuda M, Fujimoto A, Watashi K, Aizaki H, Kato T, Moriishi K, Tamura K, Takahashi Y, Wakita T, Muramatsu M, Suzuki R
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Establishment of a model for the quantification of hepatitis B virus cccDNA dynamics (2018)
  • Author(s): Kakizoe Y, Iwamoto M, Davenport MP, Watashi K, Iwami S
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] A comparison between HCV JFH-1 and Jc1 strains by quantitative analysis of infection dynamics (2018)
  • Author(s): Iwanani S, Ohashi H, Asai Y, Watashi K, Iwami S
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] HCV genome and abnomal oraganelles in the liver after elimination of hepatitis C virus by drug treatment (2018)
  • Author(s): Aizaki H, Aoyagi H, Iijima H, Zheng X, Matsuda M, Watashi K, Suzuki R, Masaki T, Shimada N, Kato K, Tsubota A, Saito T, Hayashi K, Enomoto M, Mimata A, Sakamaki Y, Ichinose S, Wakae K, Muramatsu M, Wakita T
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Identification of aryl hydrocarbon receptor ligands inhibiting the lipid accumulation and hepatitis C virus production (2018)
  • Author(s): Nishioka K, Ohashi H, Suzuki R, Aizaki H, Muramatsu M, Wakita T, Watashi K
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Drug screening for suppression of lipogenesis through downregulation of C/EBPa (2018)
  • Author(s): Satoh S, Onomura D, Watashi K, Ueda Y, Dansako H, Honda M, Kaneko S, Kato N
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Bardoxolon methyl suppresses the prolifieration of both hepatitis B and C viruses in culture cells (2018)
  • Author(s): Akahori Y, Okamura H, Sasaki M, Hasegawa H, Watashi K, Wakita T, Tanaka Y, Nio Y, Hijikata M
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Mechanistical study of antiviral activity of snake venom sPLA2 against HBV and HCV (2018)
  • Author(s): Miyayama Y, Chen M, Aoki-Utsubo C, Deng L, Shindo K, Noda T, Kohara M, Watashi K, Wakita T, Hijikata M, Hotta H
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Identification of novel HBV entry inhibitors by in vitro technologies (2018)
  • Author(s): Koichi Watashi
  • Organizer: 6th Taiwan-Japan-Korea HBV Research Symposium 2018
  • Int'l Joint Research
• [Presentation] B型肝炎ウイルス侵入阻害ペプチドの同定とその機序の解析 (2018)
  • Author(s): 深野顕人、Passioura Toby、志村聡美、佐宗若奈、森下了、小笠原裕樹、田中靖人、溝上雅史、Sureau Camille、菅裕明、脇田隆字、渡士幸一
  • Organizer: 第15回ウイルス学キャンプin湯河原
• [Presentation] B型肝炎ウイルス侵入に関わる宿主因子の同定と作用機序解析 (2018)
  • Author(s): Wakana Saso, Masashi Iwamoto, Masamichi Muramatsu, Tetsuro Matano, Koichi Watashi
  • Organizer: 第15回ウイルス学キャンプin湯河原
• [Presentation] ウイルス-脂質相互作用に関わる核内受容体の解析 (2018)
  • Author(s): Kazane Nishioka, Hirofumi Ohashi, Ryosuke Suzuki, Hideki Aizaki, Masamichi Muramatsu, Takaji Wakita, Koichi Watashi
  • Organizer: 第15回ウイルス学キャンプin湯河原
• [Presentation] D型肝炎ウイルス生存戦略の理解と意義について (2018)
  • Author(s): 岩本将士, 岩見真吾, 渡士幸一
  • Organizer: 第15回ウイルス学キャンプin湯河原
• [Presentation] Oligomerization of NTCP induces hepatitis B virus internalization (2018)
  • Author(s): Kento Fukano, Senko Tsukuda, Mio Ohki, Sam-Yong Park, Ryosuke Suzuki, Hideki Aizaki, Masamichi Muramatsu, Takaji Wakita, Yuki Ogasawara, Koichi Watashi
  • Organizer: 2018 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
  • Int'l Joint Research
• [Presentation] AlphaScreen assay targeting the NTCP-large surface antigen interaction identified rapamycin and its derivatives as novel hepatitis B virus entry inhibitors (2018)
  • Author(s): Wakana Saso, Senko Tsukuda, Hirofumi Ohashi, Kento Fukano, Ryo Morishita, Satoko Matsunaga, Mio Ohki, Akihide Ryo, Sam-Yong Park, Ryosuke Suzuki, Hideki Aizaki, Masamichi Muramatsu, Camille Sureau, Takaji Wakita, Tetsuro Matano, Koichi Watashi
  • Organizer: 2018 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
  • Int'l Joint Research
• [Presentation] Ultrastructure of hepatocytes in chronic hepatitis B patients (2018)
  • Author(s): Haruyo Aoyagi, Hiroki Iijima, Xin Zheng, Yu Ting Kao, Koichi Watashi, Ryosuke Suzuki, Noritomo Shimada, Keizo Kato, Akihito Tsubota, Ayako Mimata, Yuriko Sakamaki, Shizuko Ichinose, Kenjiro Wake, Masamichi Muramatsu, Takaji Wakita, Hideki Aizaki
  • Organizer: 2018 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
  • Int'l Joint Research
• [Presentation] Retrotransposon elements are among initial sites of HBV integration into human genome in HBV-HepG2-NTCP cell infection model (2018)
  • Author(s): Thomas Michalak, Ranjit Chauhan, Yoshimi Shimizu, Koichi Watashi, Takaji Wakita, Masayoshi Fukasawa
  • Organizer: 2018 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
  • Int'l Joint Research
• [Presentation] RNA granule components regulate HBV replication (2018)
  • Author(s): Yasuo Ariumi, Koichi Watashi, Mikinori Ueno, Lin Deng, Hak Hotta, Takaji Wakita
  • Organizer: 2018 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
  • Int'l Joint Research
• [Presentation] Rosmarinic acid is a novel inhibitor for Hepatitis B virus replication targeting viral epsilon RNA-polymerase binding (2018)
  • Author(s): Yuta Tsukamoto, Sotaro Ikeda, Koji Uwai, Riho Taguchi, Kazuaki Chayama, Takemasa Sakaguchi, Ryo Narita, Wan-Ling Yao, Fumihiko Takeuchi, Yukie Otakaki, Koichi Watashi, Takaji Wakita, Hiroki Kato, Takashi Fujita
  • Organizer: 2018 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
  • Int'l Joint Research
• [Presentation] Engineering of HBV-specific SynNotch receptor to estabilsh biosensor cells (2018)
  • Author(s): Satoko Matsunaga, Kei Miyakawa, Sayaka Shizukuishi, Koichi Watashi, Takaji Wakita, Akihide Ryo
  • Organizer: 2018 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
  • Int'l Joint Research
• [Presentation] Anti-HBV activity of novel pyrimidotriazinone derivatives through the inhibition of viral nucleocapsid assembly (2018)
  • Author(s): Masaaki Toyama, Norikazu Sakakibara, Mika Okamoto, Masanori Ikeda, Koichi Watashi, Takaji Wakita, Masanori Baba
  • Organizer: 2018 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
  • Int'l Joint Research
• [Presentation] Interaction between nuclear factor-erythroid 2 related factor 2 and hepatitis B virus (2018)
  • Author(s): Yohei Miyayama, Hitomi Okamura, Machiko Sasai, Yuichi Akahori, Koichi Watashi, Takaji Wakita, Makoto Hijikata
  • Organizer: 2018 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
  • Int'l Joint Research
• [Presentation] Acidic polysaccharides isolated from marine algae, ascophyllan and fucoidans, inhibit the early step of hepatitis B virus infection (2018)
  • Author(s): Mikinori Ueno, Masato Nogawa, Rokeya Siddiqui, Koichi Watashi, Takaji Wakita, Takasi Okimura, Shogo Isaka, Tatsuya Oda, Yasuo Ariumi
  • Organizer: 2018 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
  • Int'l Joint Research
• [Presentation] Comparative analysis of antiviral activity of sPLA2 against HBV and HCV (2018)
  • Author(s): Hak Hotta, Ming Chen, Chie Aoki-Utsubo, Lin Deng, Yohei Miyayama, Makoto Hijikata, Keiko Shindo, Takeshi Noda, Michinori Kohara, Koichi Watashi, Takaji Wakita
  • Organizer: 2018 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
  • Int'l Joint Research
• [Presentation] Flavivirus subviral particles-based DNA vaccine induces neutralizing antibodies against HCV (2018)
  • Author(s): Yato K, Matsuda M, Watanabe N, Nakajima S, Fujimoto A, Watashi K, Aizaki H, Kato T, Muramatsu M, Wakita T, Suzuki R
  • Organizer: 25th International Symposium on Hepatitis C Virus and Related Viruses
  • Int'l Joint Research
• [Presentation] Identification of Aryl hydrocarbon receptor ligands inhibiting the lipid accumulation and Hepatitis C virus production (2018)
  • Author(s): Nishioka K, Ohashi H, Suzuki R, Aizaki H, Muramatsu M, Wakita T, Watashi K
  • Organizer: 25th International Symposium on Hepatitis C Virus and Related Viruses
  • Int'l Joint Research
• [Presentation] Abnormal hepatocellular organelles remain to be observed in sustained virological response (SVR) patients (2018)
  • Author(s): Aoyagi H, Iijima H, Zheng X, Kao YT, Matsuda M, Watashi K, Suzuki R, Masaki T, Shimada N, Kato K, Tsubota A, Wake K, Wakita T, Aizaki H
  • Organizer: 25th International Symposium on Hepatitis C Virus and Related Viruses
  • Int'l Joint Research
• [Presentation] Antiviral activity of phospholipase A2 group V (PLA2G5) against HCV (2018)
  • Author(s): Puig-Basagoiti F, Fukasawa M, Suzuki R, Watashi K, Muramatsu M, Wakita T, Aizaki H
  • Organizer: 25th International Symposium on Hepatitis C Virus and Related Viruses
  • Int'l Joint Research
• [Presentation] IL-1b/ATF3 mediated regulation of HBx mRNA decay (2018)
  • Author(s): Aly HH, Watashi K, Watanabe N, Wakita T
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Acidic polysaccharides isolated from marine algae, ascophyllan and fucoidans, inhibit the early step pf hepatits B virus infection (2018)
  • Author(s): Ueno M, Nogawa M, Siddiqui R, Watashi K, Wakita T, Okimura T, Isaka S, Oda T, Ariumi Y
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Identification of host kinases that regulate hepatitis B virus internalization (2018)
  • Author(s): Iwamoto M, Saso W, Sugiyama M, Ishii K, Suzuki R, Aizaki H, Ryo A, Ohtani N, Muramatsu M, Iwami S, Tanaka Y, Wakita T, Watashi K
  • Organizer: The 66th Annual Meeting of the Japanese Society for Virology
• [Presentation] Isolation and structure determination of antiviral natural products from fungi (2018)
  • Author(s): Kamisuki S, Matsunaga H, Nishikori S, Takemoto K, Kaneko M, Nakajima S, Murakami M, Murakami H, Kuramochi K, Watashi K, Sugawara F
  • Organizer: American Society of Pharmacognosy 2018 Annual Meeting
  • Int'l Joint Research
• [Presentation] Novel predictors of the treatment outcome of Hepatitis B patients treated with entecavir and lamivudine nucleos(t)ide analogues (2018)
  • Author(s): Alexey Martyushev, Shingo Iwami, Koichi Watashi
  • Organizer: 2018 Annual Meeting of the Society for Mathematical Biology & the Japanese Society for Mathematical Biology
  • Int'l Joint Research
• [Patent(Industrial Property Rights)] HBV感染阻害剤 (2019)
  • Inventor(s): 渡士幸一、脇田隆字、村松正道
  • Industrial Property Rights Holder: 渡士幸一、脇田隆字、村松正道
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 特願2019-033601