Analysis of regulation mechanisms of hepatitis B virus life cycle by kinases and post-translational modifications

2016 Fiscal Year Research-status Report

• Project/Area Number: 26460565
• 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): 2014-04-01 – 2018-03-31
• Keywords: B型肝炎ウイルス

Outline of Annual Research Achievements

B型肝炎ウイルス(HBV)複製培養系を用いて、細胞骨格がHBV coreタンパク質の多量体化を制御していることが示唆された。またHBV coreタンパク質が細胞骨格構成タンパク質のひとつと相互作用しており、この細胞骨格上に高頻度に局在していることが認められた。細胞骨格破壊を誘発することにより、この相互作用に解離が見られ、またHBV coreタンパク質の多量体化および複製レベルの低下が認められた。一方、HBV複製細胞株からHBV高複製クローンと低複製細胞クローンを得たが、これらの細胞においてはcoreタンパク質と細胞骨格の相互作用が異なっており、HBV高複製細胞クローンでその相互作用が顕著であった。これらの結果は、coreタンパク質と細胞骨格の相互作用がHBV複製レベルを規定する一つの要因であることを示唆している。またこれらの制御機構に細胞骨格因子の翻訳後修飾が影響を与えていることを示唆する結果を得た。
またHBV感染培養系を用いて、HBV感染の特に侵入過程を阻害するキナーゼ阻害剤を同定した。このキナーゼ阻害剤の存在下ではHBVだけではなくD型肝炎ウイルスの侵入も阻害されることが明らかとなった。
以上のようにHBV感染複製にリン酸化等のタンパク質修飾が重要な役割を果たしていることが示唆された。これらの知見は新たな抗ウイルス薬創出に重要な情報を提供するものである。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

本研究により、HBV感染複製活性には宿主タンパク質修飾が重要であることが示唆された。当初研究目的としていた、ウイルス感染におけるリン酸化等タンパク質修飾の役割に関しては解析が進み新知見が得られた。

Strategy for Future Research Activity

今後は宿主細胞内のHBV coreタンパク質が細胞骨格をどのように利用して多量体化を可能としているのか、詳細なメカニズムの解明が望まれる。またHBVの侵入過程において宿主タンパク質のリン酸化がどのようにHBV感染効率を上昇させているかの機序解析も興味深いところである。

Causes of Carryover

これまでPKCがHBVの内在化に関与すること、PKC特異的キナーゼ阻害剤がHBV感染を抑制することを見出してきた。今後さらにHBVの宿主PKC発現・活性への影響、PKCによるHBV内在化制御機構を調べることで、その生理的意義が解明され、より独創性、意義が大きい論文の投稿が可能となり、本研究目的をより精緻に達成できる。またこれまでの研究が効率的に進み直接経費が節約できたため、上記の研究を追加で行う。

Expenditure Plan for Carryover Budget

残りの研究費で、PKCによるHBV内在化メニズム、PKC特異的キナーゼ阻害剤のHBV感染抑制効果、HBVの宿主PKC発現・活性への影響、を調べ、より独創性、意義が大きい研究とする。

Research Products

• [Int'l Joint Research] Los Alamos National Laboratory/SCYNEXIS, Inc./University of Chicago(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: Los Alamos National Laboratory/SCYNEXIS, Inc./University of Chicago
  • # of Other Institutions: 1
• [Int'l Joint Research] INTS(フランス)
  • Country Name: FRANCE
  • Counterpart Institution: INTS
• [Int'l Joint Research] Erasmus MC-University Medical Center(オランダ)
  • Country Name: NETHERLANDS
  • Counterpart Institution: Erasmus MC-University Medical Center
• [Int'l Joint Research] National Taiwan University(台湾)
  • Country Name: その他の国・地域
  • Counterpart Institution: National Taiwan University
• [Journal Article] Reply to Padmanabhan and Dixit: Hepatitis C virus entry inhibitors for optimally boosting direct-acting antiviral-based treatments (2017)
  • Author(s): Ohashi H, Koizumi Y, Fukano K, Wakita T, Perelson AS, Iwami S, Watashi K*
  • Journal Title: Proc Natl Acad Sci USA Volume: NA Pages: NA
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Hepatitis B virus prevents excessive viral production via reduction of cell-death inducing DFF45-like effectors (2017)
  • Author(s): Yasumoto J, Kasai H, Yoshimura K, Otoguro T, Watashi K, Wakita T, Yamashita A, Tanaka T, Takeda S, Moriishi K
  • Journal Title: J Gen Virol Volume: NA Pages: NA
  • Peer Reviewed
• [Journal Article] Establishment of a human hepatocellular cell line capable of maintaining long-term replication of hepatitis B virus (2017)
  • Author(s): Yao WL, Ikeda S, Tsukamoto Y, Shindo K, Otakaki Y, Qin M, Iwasawa Y, Takeuchi F, Kaname Y, Chou YC, Chang C, Watashi K, Wakita T, Noda T, Kato H, Fujita T
  • Journal Title: Int Immunol Volume: NA Pages: NA
  • DOI: 10.1093/intimm/dxx012
  • Peer Reviewed
• [Journal Article] Stereo-controlled synthesis of functionalized tetrahydropyridines based on the cyanomethylation of 1,6-dihydropyridines and generation of anti-hepatitis C virus agents (2017)
  • Author(s): Watanabe R, Mizoguchi H, Oikawa H, Ohashi H, Watashi K, Oguri H
  • Journal Title: Bioorg Med Chem Volume: NA Pages: NA
  • DOI: 10.1016/j.bmc.2017.03.011
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Human induced-pluripotent stem cell-derived hepatocyte-like cells as an in vitro model of human hepatitis B virus infection (2017)
  • Author(s): Sakurai F, Mitani S, Yamamoto T, Takayama K, Tachibana M, Watashi K, Wakita T, Iijima S, Tanaka Y, Mizuguchi H
  • Journal Title: Sci Rep Volume: 7 Pages: 45698
  • DOI: 10.1038/srep45698
  • Peer Reviewed / Open Access
• [Journal Article] Gut microbiota promotes obesity-associated liver cancer through PGE2-mediated suppression of antitumor immunity (2017)
  • Author(s): Loo TM, Kamachi F, Watanabe Y, Yoshimoto S, Kanda H, Arai Y, Nakajima-Takagi Y, Iwama A, Koga T, Sugimoto Y, Ozawa T, Nakamura M, Kumagai M, Watashi K, Taketo MM, Aoki T, Narumiya S, Oshima M, Arita M, Hara E, Ohtani N
  • Journal Title: Cancer Discov Volume: 7 Pages: 522-538
  • DOI: 10.1158/2159-8290.CD-16-0932
  • Peer Reviewed
• [Journal Article] Quantifying antiviral activity optimizes drug combinations against hepatitis C virus infection (2017)
  • Author(s): Koizumi Y, Ohashi H, Nakajima S, Tanaka Y, Wakita T, Perelson AS, Iwami S, Watashi K*
  • Journal Title: Proc Natl Acad Sci USA Volume: 114 Pages: 1922-1927
  • DOI: 10.1073/pnas.1610197114
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Cyclosporin derivatives inhibit hepatitis B virus entry without interfering the NTCP transporter (2017)
  • Author(s): Shimura S, Watashi K*, Fukano K, Peel M, Sluder A, Kawai F, Iwamoto M, Tsukuda S, Takeuchi JS, Miyake T, Sugiyama M, Ogasawara Y, Park SY, Tanaka Y, Kusuhara H, Mizokami M, Sureau C, Wakita T
  • Journal Title: J Hepatol Volume: 66 Pages: 685-692
  • DOI: 10.1016/j.jhep.2016.11.009
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A new class of hepatitis B and D virus entry inhibitors, proanthocyanidin and its analogs, that directly act on the viral large surface proteins (2017)
  • Author(s): Tsukuda S, Watashi K*, Hojima T, Isogawa M, Iwamoto M, Omagari K, Suzuki R, Aizaki H, Kojima S, Sugiyama M, Saito A, Tanaka Y, Mizokami M, Sureau C, Wakita T
  • Journal Title: Hepatology Volume: 65 Pages: 1104-1116
  • DOI: 10.1002/hep.28952
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Host factor PRPF31 is involved in cccDNA production in HBV-replicating cells (2017)
  • Author(s): Kinoshita W, Ogura N, Watashi K, Wakita T
  • Journal Title: Biochem Biophys Res Commun Volume: 482 Pages: 638-644
  • DOI: 10.1016/j.bbrc.2016.11.085
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Hepatitis B virus X protein impairs α-interferon signaling via upregulation of suppressor of cytokine signaling 3 and protein phosphatase 2A (2017)
  • Author(s): Tsunematsu S, Suda G, Yamasaki K, Kimura M, Izumi T, Umemura M, Ito J, Sato F, Nakai M, Sho T, Morikawa K, Ogawa K, Tanaka Y, Watashi K, Wakita T, Sakamoto N
  • Journal Title: J Med Virol Volume: 89 Pages: 267-275
  • DOI: 10.1002/jmv.24643
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 抗Ｂ型肝炎ウイルス薬の現状と新規薬剤開発のアプローチ (2017)
  • Author(s): 九十田千子, 渡士幸一
  • Journal Title: 化学療法の領域 Volume: 33 Pages: 73-78
• [Journal Article] Isolation and characterization of hepatitis C virus resistant to a novel phenanthridinone derivative (2016)
  • Author(s): Ito W, Toyama M, Okamoto M, Ikeda M, Watashi K, Wakita T, Hashimoto Y, Baba M
  • Journal Title: Antivir Chem Chemother Volume: 24 Pages: 148-154
  • DOI: 10.1177/2040206616663956
  • Peer Reviewed
• [Journal Article] Closing the door on hepatitis B and D virus entry: what are our therapeutic options? (2016)
  • Author(s): Iwamoto M, Watashi K*
  • Journal Title: Future Virology Volume: 11 Pages: 715-718
  • DOI: 10.2217/fvl-2016-0097
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Fungus-derived neoechinulin B as a novel antagonist of liver X receptor, identified by chemical genetics using a hepatitis C virus cell culture system (2016)
  • Author(s): Nakajima S, Watashi K*, Ohashi H, Kamisuki S, Izaguirre-Carbonell J, Kwon ATJ, Suzuki H, Kataoka M, Tsukuda S, Okada M, Moi ML, Takeuchi T, Arita M, Suzuki R, Aizaki H, Kato T, Suzuki T, Hasegawa H, Takasaki T, Sugawara F, Wakita T
  • Journal Title: J Virol Volume: 90 Pages: 9058-9074
  • DOI: 10.1128/JVI.00856-16
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Interferon-stimulated gene of 20KDa protein (ISG20) degrades RNA of hepatitis B virus to impede the replication of HBV in vitro and in vivo (2016)
  • Author(s): Leong CR, Funami K, Oshiumi H, Mengao D, Takaki H, Matsumoto M, Ali HH, Watashi K, Chayama K, Seya T
  • Journal Title: Oncotarget Volume: 7 Pages: 68179-681193
  • DOI: 10.18632/oncotarget
  • Peer Reviewed
• [Journal Article] Human induced pluripotent stem cell-derived hepatic cell lines as a new model for host interaction with hepatitis B virus (2016)
  • Author(s): Kaneko S, Kakinuma S, Asahina Y, Kamiya A, Miyoshi M, Tsunoda T, Nitta S, Asano Y, Nagata H, Otani S, Kawai-Kitahata F, Murakawa M, Itsui Y, Nakagawa M, Azuma S, Nakauchi H, Nishitsuji H, Ujino S, Shimotohno K, Iwamoto M, Watashi K, Wakita T, Watanabe M
  • Journal Title: Sci. Rep Volume: 6 Pages: 29358
  • DOI: 10.1038/srep29358
  • Peer Reviewed / Open Access
• [Journal Article] HBV slow maturation process leading to infection (2016)
  • Author(s): Watashi K*
  • Journal Title: Trends Microbiol Volume: 24 Pages: 597-599
  • DOI: 10.1016/j.tim.2016.06.007
  • Peer Reviewed
• [Journal Article] Bivalent vaccine platform based on Japanese encephalitis virus (JEV) elicit neutralizing antibodies against JEV and hepatitis C virus (2016)
  • Author(s): Saga R, Fujimoto A, Watanabe N, Matsuda M, Hasegawa M, Watashi K, Aizaki H, Nakamura N, Tajima S, Takasaki T, Konishi E, Kato T, Kohara M, Takeyama H, Wakita T, Suzuki R
  • Journal Title: Sci Rep Volume: 6 Pages: 28688
  • DOI: 10.1038/srep28688
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] RNA exosome complex regulates stability of Hepatitis B Virus’s X-mRNA transcript in a Non-Stop mediated (NSD) RNA quality control mechanism (2016)
  • Author(s): Aly HH, Suzuki J, Watashi K, Chayama K, Hoshino S, Hijikata M, Kato T, Wakita T
  • Journal Title: J Biol Chem Volume: 291 Pages: 15958-15974
  • DOI: 10.1074/jbc.M116.724641
  • Peer Reviewed
• [Journal Article] Fatty acid biosynthesis is involved in the production of hepatitis B virus particles (2016)
  • Author(s): Okamura H, Nio Y, Akahori Y, Kim S, Watashi K, Wakita T, Hijikata M
  • Journal Title: Biochem Biophys Res Commun Volume: 475 Pages: 87-92
  • DOI: 10.1016/j.bbrc.2016.05.043
  • Peer Reviewed
• [Journal Article] Disparity of basal and therapeutically activated interferon signalling in constraining hepatitis E virus infection (2016)
  • Author(s): Zhou X, Xu L, Wang W, Watashi K, Wang Y, Sprengers D, de Ruiter PE, van der Laan LJ, Metselaar HJ, Kamar N, Peppelenbosch MP, Pan Q
  • Journal Title: J Viral Hepat Volume: 23 Pages: 294-304
  • DOI: 10.1111/jvh.12491
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Single-domain Intrabodies against HCV Core Inhibit Viral Propagation and Core-induced NF-kappaB Activation (2016)
  • Author(s): Suzuki R, Saito K, Matsuda M, Sato M, Kanegae Y, Shi G, Watashi K, Aizaki H, Chiba J, Saito I, Wakita T, Suzuki T
  • Journal Title: J Gen Virol Volume: 97 Pages: 887-892
  • DOI: 10.1099/jgv.0.000423
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Ｂ型肝炎ウイルス研究のトピックス (2016)
  • Author(s): 渡士幸一, 相崎英樹
  • Journal Title: 小児科 Volume: 57 Pages: 1107-1111
• [Presentation] ヒトiPS細胞由来肝細胞のB型肝炎ウイルス in vitro 感染評価系への応用 (2017)
  • Author(s): 三谷 成二, 櫻井 文教, 山本 達郎, 高山 和雄, 立花 雅史, 渡士 幸一, 脇田 隆字, 飯島 沙幸, 田中 靖人, 水口 裕之
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-24 – 2017-03-27
• [Presentation] B型肝炎ウイルスの侵入受容体の解析とその新規阻害剤の同定 (2017)
  • Author(s): 深野 顕人, 志村 聡美, Michael PEEL, Ann SLUDER, 河合 文啓, 九十田 千子, 鈴木 亮介, 相 崎 英樹, 朴 三用, 脇田 隆字, 小笠原 裕樹, 渡士 幸一
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-24 – 2017-03-27
• [Presentation] Ultrastructure of hepatocytes in chronic hepatitis C patients who achieve a sustained virological response (2017)
  • Author(s): Aoyagi H, Iijima H, Puig-Basagoiti F, Zheng X, Kao YT, Hossam GE, 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 26th of Conference of Asian Pacific Association for the Study of the Liver, ANNUAL MEETING 2017
  • Place of Presentation: 上海
  • Year and Date: 2017-02-15 – 2017-02-19
  • Int'l Joint Research
• [Presentation] Acute Hepatitis B in Japan, April 1999 ~ December 2015 (2017)
  • Author(s): Zheng X, Aoyagi H, Hossam GE, Zaitsu T, Puig-Basagoiti F, Kao YT, Watashi K, Suzuki R, Takahashi T, Sunagawa T, Oishi K, Wakita T, Aizaki H
  • Organizer: The 26th of Conference of Asian Pacific Association for the Study of the Liver, ANNUAL MEETING 2017
  • Place of Presentation: 上海
  • Year and Date: 2017-02-15 – 2017-02-19
  • Int'l Joint Research
• [Presentation] Mechanism of HBV entry and the role of NTCP (2016)
  • Author(s): Watashi K
  • Organizer: APASL Single Topic Conference (STC) - 6th HBV Conference
  • Place of Presentation: 北京
  • Year and Date: 2016-12-16 – 2016-12-18
  • Int'l Joint Research / Invited
• [Presentation] A novel tricyclic polyketide, vanitaracin A, specifically inhibits the entry of hepatitis B and D viruses through targeting NTCP (2016)
  • Author(s): Kaneko M, Watashi K, Kamisuki S, Matsunaga H, Iwamoto M, Kawai F, Ohashi H, Tsukuda S, Shimura S, Suzuki R, Aizaki H, Sugiyama M, Sam-Yong Park, Ito T, Ohtani N, Sugawara F, Tanaka Y, Mizokami M, Sureau C, Wakita T
  • Organizer: 東京理科大学イメージングフロンティアセンターシンポジウム
  • Place of Presentation: 野田
  • Year and Date: 2016-12-10 – 2016-12-10
• [Presentation] B型肝炎ウイルス侵入過程を標的とした創薬研究 (2016)
  • Author(s): 渡士幸一、九十田千子、脇田隆字
  • Organizer: 第41回日本肝臓学会東部会
  • Place of Presentation: 東京
  • Year and Date: 2016-12-08 – 2016-12-09
• [Presentation] Protein kinase C triggers the internalization of hepatitis B and D viruses into hepatocytes (2016)
  • Author(s): Iwamoto M, Kaneko M, Ohashi H, Kawai F, Suzuki R, Aizaki H, Park SY, Ryo A, Ohtani N, Wakita T, Watashi K
  • Organizer: The 64th Annual Meeting of the Japanese Society for Virology
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23 – 2016-10-25
• [Presentation] Strategy for hepatitis B and D virus entry inhibition without impairing NTCP-mediated bile acid uptake (2016)
  • Author(s): Watashi K, Shimura S, Peel M, Sluder A, Kawai F, Iwamoto M, Tsukuda S, Suzuki R, Aizaki H, Sugiyama M, Park SY, Tanaka Y, Mizokami M, Wakita T
  • Organizer: The 64th Annual Meeting of the Japanese Society for Virology
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23 – 2016-10-25
• [Presentation] Fatty acid biosynthesis specifically regulates hepatitis B virus particle production (2016)
  • Author(s): Okamura H, Akahori Y, Nio Y, Watashi K, Wakita T, Hijikata M
  • Organizer: The 64th Annual Meeting of the Japanese Society for Virology
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23 – 2016-10-25
• [Presentation] Non-Stop mediated RNA decay mechanism targets HBV-X mRNA for degradation at the RNA exosome (2016)
  • Author(s): Aly H, Watashi K, Chayama K, Hijikata M, Wakita T
  • Organizer: The 64th Annual Meeting of the Japanese Society for Virology
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23 – 2016-10-25
• [Presentation] Development of novel hepatitis B virus culture system using immortalized human hepatocytes (2016)
  • Author(s): Akahori Y, Kato H, Fujita T, Moriishi K, Watashi K, Wakita T, Hijikata M
  • Organizer: The 64th Annual Meeting of the Japanese Society for Virology
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23 – 2016-10-25
• [Presentation] ISG20 inhibits HBV replication by accelerating decay of HBV genome (2016)
  • Author(s): Funami K, Leong CR, Oshiumi H, Okamoto M, Takaki H, Matsumoto M, Chayama K, Watashi K, Seya T
  • Organizer: The 64th Annual Meeting of the Japanese Society for Virology
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23 – 2016-10-25
• [Presentation] Development of a neutralization assay for multiple flaviviruses based on single-round infectious particles (2016)
  • Author(s): Matsuda M, Yamanaka A, Yoshii K, Watashi K, Aizaki H, Konishi E, Takasaki T, Wakita T, Suzuki R
  • Organizer: The 64th Annual Meeting of the Japanese Society for Virology
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23 – 2016-10-25
• [Presentation] Characterization of origomeric flavonoids as a novel class of anti-HBV entry inhibitors that directly target viral envelope protein (2016)
  • Author(s): Tsukuda S, Watashi K, Hojima T, Isogawa M, Suzuki R, Aizaki H, Kojima S, Sugiyama M, Saito A, Tanaka Y, Mizokami M, Wakita T
  • Organizer: The 64th Annual Meeting of the Japanese Society for Virology
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23 – 2016-10-25
• [Presentation] Aryl hydrocarbon receptor regulates the assembly of hepatitis C virus and affects the emergence of drug resistant virus against DAAs (2016)
  • Author(s): Ohashi H, Syo Nakajima, Sulyi Kim, Suzuki R, Aizaki H, Fukasawa M, Kamisuki S, Sugawara F, Ohtani N, Wakita T, Watashi K
  • Organizer: The 64th Annual Meeting of the Japanese Society for Virology
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23 – 2016-10-25
• [Presentation] Analysis of the HBV life cycle in a HepG2 expressing human NTCP (2016)
  • Author(s): Rahayu R, Ohsaki E, Okamoto T, Watashi K, Ueda K
  • Organizer: The 64th Annual Meeting of the Japanese Society for Virology
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23 – 2016-10-25
• [Presentation] Sphingomyelin is a component in the membranous replication factories (2016)
  • Author(s): Gewaid HE, Aoyagi H, Watashi K, Suzuki R, Aly HH, Kumajai K, Yamaji T, Fukasawa M, Mimata A, Sakamaki Y, Ichinose S, Hanada K, Wakita T, Aizaki H
  • Organizer: 23rd International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: 京都
  • Year and Date: 2016-10-11 – 2016-10-15
  • Int'l Joint Research
• [Presentation] The HCV cell culture system identified fungal-derived neoechinulin B as a novel antagonist of liver X receptor (2016)
  • Author(s): Watashi K, Nakajima S, Ohashi H, Kamisuki S, Kwon ATJ, Suzuki H, Tsukuda S, Suzuki R, Aizaki H, Kato T, Sugawara F, Wakita T
  • Organizer: 23rd International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: 京都
  • Year and Date: 2016-10-11 – 2016-10-15
  • Int'l Joint Research
• [Presentation] Vanitaracin A is a novel entry inhibitor of hepatitis B and D viruses through targeting NTCP (2016)
  • Author(s): Kaneko M, Watashi K, Kamisuki S, Iwamoto M, Tsukuda S, Ohashi H, Kawai F, Mizokami M, Park SY, Tanaka Y, Suzuki R, Aizaki H, Sugawara F, Otani N, Wakita T
  • Organizer: 23rd International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: 京都
  • Year and Date: 2016-10-11 – 2016-10-15
  • Int'l Joint Research
• [Presentation] Retinoid inhibitors abolish the host permissiveness to hepatitis B virus infection by modulating the expression of NTCP (2016)
  • Author(s): Tsukuda S, Watashi K, Iwamoto M, Suzuki R, Aizaki H, Kojima S, Sugiyama M, Tanaka Y, Mizokami M, Wakita T
  • Organizer: 23rd International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: 京都
  • Year and Date: 2016-10-11 – 2016-10-15
  • Int'l Joint Research
• [Presentation] Establishment of the method for evaluating molecular interaction between hepatitis B virus entry inhibitors and sodium taurocholate cotransporting polypeptide (2016)
  • 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: 23rd International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: 京都
  • Year and Date: 2016-10-11 – 2016-10-15
  • Int'l Joint Research
• [Presentation] Non-Stop mediated RNA decay mechanism regulates Hepatitis B virus replication (2016)
  • Author(s): Aly HH, Watashi K, Chayama K, Wakita T
  • Organizer: 23rd International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: 京都
  • Year and Date: 2016-10-11 – 2016-10-15
  • Int'l Joint Research
• [Presentation] Role of lipid droplets in the emergence of drug resistant virus against direct acting antivirals (2016)
  • Author(s): Ohashi H, Nakajima S, Kim S, Suzuki R, Aizaki H, Fukasawa F, Kamisuki S, Sugawara F, Ohtani N, Wakita T, Watashi K
  • Organizer: 23rd International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: 京都
  • Year and Date: 2016-10-11 – 2016-10-15
  • Int'l Joint Research
• [Presentation] Hepatitis B virus capsid formation is regulated by microtubules and their posttranslational modification (2016)
  • Author(s): Iwamoto M, Sugiyama M, Suzuki R, Aizaki H, Tanaka Y, Mizokami M, Ohtani N, Wakita T, Watashi K
  • Organizer: 23rd International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: 京都
  • Year and Date: 2016-10-11 – 2016-10-15
  • Int'l Joint Research
• [Presentation] Development of Novel Anti-viral Agents against Hepatitis B Virus by using an siRNA Screening Panel Targeting the Carbohydrate Synthesis System (2016)
  • Author(s): Ito K, Yoneda M, Angata K, Watashi K, Wakita T, Tanaka Y, Mizokami M, Narimatsu H
  • Organizer: 23rd International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: 京都
  • Year and Date: 2016-10-11 – 2016-10-15
  • Int'l Joint Research
• [Presentation] Human hepatic stellate cells are permissive for hepatitis C virus infection/replication and play important roles in fibrosis (2016)
  • Author(s): Zaitsu T, Aoyagi H, Matsuda M, Watanabe N, Fujimoto A, Watashi K, Suzuki R, Fukuhara T, Matsuura M, Wake K, Suzuki T, Matsuura T, Tamura K, Wakita T, Aizaki H
  • Organizer: 23rd International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: 京都
  • Year and Date: 2016-10-11 – 2016-10-15
  • Int'l Joint Research
• [Presentation] Activation of protein kinase R by hepatitis C virus RNA-dependent RNA polymerase (2016)
  • Author(s): Suzuki R, Matsuda M, Shimoike T, Watashi K, Aizaki H, Kato T, Suzuki T, Wakita T
  • Organizer: 23rd International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: 京都
  • Year and Date: 2016-10-11 – 2016-10-15
  • Int'l Joint Research
• [Presentation] Multiple flaviviruses neutralization assay based on single-round infectious particles (2016)
  • Author(s): Matsuda M, Yamanaka A, Yoshii K, Watashi K, Aizaki H, Konishi E, Takasaki T, Wakita T, Suzuki R
  • Organizer: 23rd International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: 京都
  • Year and Date: 2016-10-11 – 2016-10-15
  • Int'l Joint Research
• [Presentation] 肝炎ウイルスの基礎研究から創薬研究へ (2016)
  • Author(s): 渡士幸一
  • Organizer: 明治薬科大学セミナー
  • Place of Presentation: 東京
  • Year and Date: 2016-09-27 – 2016-09-27
  • Invited
• [Presentation] Strategy for hepatitis B and D virus entry inhibition without affecting bile acid transport (2016)
  • Author(s): Watashi K, Shimura S, Peel M, Sluder A, Kawai F, Iwamoto M, Tsukuda S, Suzuki R, Aizaki H, Sugiyama M, Park SY, Tanaka Y, Mizokami M, Wakita T
  • Organizer: 2016 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: ソウル
  • Year and Date: 2016-09-21 – 2016-09-24
  • Int'l Joint Research
• [Presentation] Proanthocyanidin and its analogs are new class of HBV and HDV entry inhibitors that target the viral preS1 region (2016)
  • Author(s): Tsukuda S, Watashi K, Hojima T, Isogawa M, Iwamoto M, Suzuki R, Aizaki H, Kojima S, Sugiyama M, Saito A, Tanaka Y, Mizokami M, Wakita T
  • Organizer: 2016 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: ソウル
  • Year and Date: 2016-09-21 – 2016-09-24
  • Int'l Joint Research
• [Presentation] Development of Novel Anti-viral Agents against Hepatitis B Virus by using an siRNA Screening Panel Targeting the Carbohydrate Synthesis (2016)
  • Author(s): Ito K, Yoneda M, Angata K, Watashi K, Wakita T, Tanaka Y, Tong S, Mizokami M, Narimatsu H
  • Organizer: 2016 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: ソウル
  • Year and Date: 2016-09-21 – 2016-09-24
  • Int'l Joint Research
• [Presentation] A novel Neplanocin A derivatives selectively inhibit HBV replication (2016)
  • Author(s): Toyama M, Hamasaki T, Okamoto M, Ikeda M, Watashi K, Wakita T, Yamashita A, Moriishi K, Sharon A, Baba M
  • Organizer: 2016 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: ソウル
  • Year and Date: 2016-09-21 – 2016-09-24
  • Int'l Joint Research
• [Presentation] The cell line derived from immortalized human hepatocytes was highly susceptible to blood-borne hepatitis B virus in the three-dimensional culture condition (2016)
  • Author(s): Akahori Y, Kato H, Fujita T, Moriishi K, Watashi K, Wakita T, Hijikata M
  • Organizer: 2016 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: ソウル
  • Year and Date: 2016-09-21 – 2016-09-24
  • Int'l Joint Research
• [Presentation] Induction of NTCP expression in a human HCC cell line by retinoic acid and its possible effect on host susceptibility to HBV infection (2016)
  • Author(s): Masaki T, Matsumoto Y, Aizaki H, Nagamori shushi, Watashi K, Park J, Kanai Y, Kojima S, Wakita T, Matsuura T
  • Organizer: 2016 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: ソウル
  • Year and Date: 2016-09-21 – 2016-09-24
  • Int'l Joint Research
• [Presentation] Non-Stop mediated RNA quality control decay regulates HBV X-mRNA (2016)
  • Author(s): Aly HH, Suzuki J, Watashi K, Hijikata M, Kato T, Chayama K, Wakita T
  • Organizer: 2016 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: ソウル
  • Year and Date: 2016-09-21 – 2016-09-24
  • Int'l Joint Research
• [Presentation] DDX3 and INI1/hSNF5 restrict HBV replication through alteration of subcellular localization of HBx (2016)
  • Author(s): Ariumi Y, Watashi K, Wakita T
  • Organizer: 2016 International HBV Meeting The Molecular Biology of Hepatitis B Viruses
  • Place of Presentation: ソウル
  • Year and Date: 2016-09-21 – 2016-09-24
  • Int'l Joint Research
• [Presentation] Protein kinase C triggers the internalization of hepatitis B and D viruses into hepatocytes (2016)
  • Author(s): Iwamoto M, Kaneko M, Ohashi H, Kawai F, Suzuki R, Aizaki H, Park SY, Ryo A, Ohtani N, Wakita T, Watashi K
  • Organizer: 第13回ウイルス学キャンプ in 湯河原
  • Place of Presentation: 湯河原
  • Year and Date: 2016-08-30 – 2016-08-31
• [Presentation] Aryl hydrocarbon receptorのC型肝炎ウイルス感染応答における役割・分子メカニズムの解析 (2016)
  • Author(s): Ohashi H, Nakajima S, Kim S, Suzuki R, Aizaki H, Fukasawa M, Kamisuki S, Sugawara F, Ohtani N, WakitaT, Watashi K
  • Organizer: 第13回ウイルス学キャンプ in 湯河原
  • Place of Presentation: 湯河原
  • Year and Date: 2016-08-30 – 2016-08-31
• [Presentation] 細胞培養系を用いた新規抗B型肝炎ウイルス化合物の同定 (2016)
  • Author(s): Kaneko M, Watashi K, Iwamoto M, Kamisuki S, Matsunaga H, Iwamoto M, Kawai F, Ohashi H, Tsukuda S, Shimura S, Suzuki R, Aizaki H, Sugiyama M, Park SY, Ito T, Ohtani N, Sugawara F, Tanaka Y, Mizokami M, Sureau C, Wakita T
  • Organizer: 第13回ウイルス学キャンプ in 湯河原
  • Place of Presentation: 湯河原
  • Year and Date: 2016-08-30 – 2016-08-31
• [Presentation] B型肝炎ウイルスの適応進化メカニズム解析 (2016)
  • Author(s): 竹内（柴田）潤子、 岩本将士、 渡士幸一
  • Organizer: 第13回ウイルス学キャンプ in 湯河原
  • Place of Presentation: 湯河原
  • Year and Date: 2016-08-30 – 2016-08-31
• [Presentation] 低分子化合物を用いたB型肝炎ウイルスの感染感受性決定機構の解析 (2016)
  • Author(s): Tsukuda S, Watashi K, Iwamoto M, Suzuki R, Aizaki H, Kojima S, Wakita T
  • Organizer: 第13回ウイルス学キャンプ in 湯河原
  • Place of Presentation: 湯河原
  • Year and Date: 2016-08-30 – 2016-08-31
• [Presentation] B型肝炎ウイルスの侵入受容体阻害剤の同定とその機序の解析 (2016)
  • 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: 第13回ウイルス学キャンプ in 湯河原
  • Place of Presentation: 湯河原
  • Year and Date: 2016-08-30 – 2016-08-31
• [Presentation] 肝炎ウイルスの創薬研究 (2016)
  • Author(s): 渡士幸一
  • Organizer: 京都大学ウイルス研究所セミナー, ウイルス研究の潮流シリーズ
  • Place of Presentation: 京都
  • Year and Date: 2016-07-13 – 2016-07-13
  • Invited
• [Presentation] Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP) (2016)
  • Author(s): 渡士幸一
  • Organizer: 第29回肝臓フォーラム（東部）
  • Place of Presentation: 東京
  • Year and Date: 2016-07-09 – 2016-07-09
  • Invited
• [Presentation] 肝炎ウイルス研究の現状と、抗ウイルス創薬研究 (2016)
  • Author(s): 渡士幸一
  • Organizer: Summer Retrovirus Conference (SRC) 2016
  • Place of Presentation: 京都
  • Year and Date: 2016-07-07 – 2016-07-08
  • Invited
• [Presentation] B型肝炎ウイルスを標的とした新規侵入阻害剤の同定と作用機序の解析 (2016)
  • Author(s): 九十田千子、渡士幸一、小嶋聡一、脇田隆字
  • Organizer: 第52回日本肝臓学会総会
  • Place of Presentation: 幕張
  • Year and Date: 2016-05-19 – 2016-05-20
• [Presentation] 新規作用機序を有するB型肝炎ウイルス創薬 (2016)
  • Author(s): 渡士幸一、九十田千子、脇田隆字
  • Organizer: 第52回日本肝臓学会総会
  • Place of Presentation: 幕張
  • Year and Date: 2016-05-19 – 2016-05-20
• [Presentation] 脂肪酸生合成経路の阻害によるHBV粒子の産生抑制機構の解析 (2016)
  • Author(s): 岡村瞳、赤堀祐一、金ソルイ、渡士幸一、脇田隆字、土方誠
  • Organizer: 第26回抗ウイルス療法学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2016-05-13 – 2016-05-15
• [Presentation] ピリミドトリアジノン誘導体の抗HBV効果について (2016)
  • Author(s): 外山政明、濱崎隆之、岡本実佳、渡士幸一、脇田隆字、馬場昌範
  • Organizer: 第26回抗ウイルス療法学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2016-05-13 – 2016-05-15
• [Presentation] B型肝炎ウイルス粒子を直接標的とする侵入阻害剤proanthocyanidin (2016)
  • Author(s): 九十田千子、渡士幸一、濱田義知、齊藤安貴子、五十川正記、田中義正、鈴木亮介、相崎英樹、小嶋聡一、杉山真也、田中靖人、溝上雅史、脇田隆字
  • Organizer: 第26回抗ウイルス療法学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2016-05-13 – 2016-05-15
• [Presentation] 立体培養したHBV受容体hNTCP発現不死化ヒト肝細胞による新たなHBV培養系を用いた抗HBV薬評価系の構築 (2016)
  • Author(s): 赤堀祐一、加藤博己、藤田尚志、森石恆司、渡士幸一、脇田隆字、土方誠
  • Organizer: 第26回抗ウイルス療法学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2016-05-13 – 2016-05-15
• [Presentation] HCVに対する抗ウイルス治療後、SVR後の肝細胞の超微細構造の変化 (2016)
  • Author(s): 青柳東代、飯島尋子、松田麻未、渡士幸一、鈴木亮介、政木隆博、坂巻有里子、市野瀬志津子、坪田昭人、和氣健二郎、脇田隆字、相崎英樹
  • Organizer: 第26回抗ウイルス療法学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2016-05-13 – 2016-05-15
• [Presentation] B型肝炎ウイルス感染を阻害する新規macrocyclesの同定と、NTCP依存性胆汁酸取り込み抑制能を欠失した選択的阻害剤の創出 (2016)
  • Author(s): 渡士幸一、志村聡美、Michael Peel、Ann Sluder、河合文啓、岩本将士、杉山真也、朴三用、田中靖人、溝上雅史、脇田隆字
  • Organizer: 第26回抗ウイルス療法学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2016-05-13 – 2016-05-15
• [Presentation] Precore stop codon regulates the stability of HBV X-mRNA (2016)
  • Author(s): Aly HH, Suzuki J, Watashi K, Chayama K, Wakita T
  • Organizer: 4th Taiwan-Korea-Japan Research Symposium on Hepatitis B Virus
  • Place of Presentation: 台北
  • Year and Date: 2016-04-09 – 2016-04-10
  • Int'l Joint Research
• [Presentation] Inhibition of HBV entry process through targeting host and viral molecules (2016)
  • Author(s): Tsukuda S, Watashi K, Hamada Y, Isogawa M, Iwamoto M, Suzuki R, Aizaki H, Kojima S, Sugiyama M, Saito A, Tanaka Y, Mizokami M, Wakita T
  • Organizer: 4th Taiwan-Korea-Japan Research Symposium on Hepatitis B Virus
  • Place of Presentation: 台北
  • Year and Date: 2016-04-09 – 2016-04-10
  • Int'l Joint Research