Establishing in vitro-in vivo HBV infection system using mouse hepatocytes

• Project/Area Number: 16K15282
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Osaka University
• Principal Investigator: Ueda Keiji 大阪大学, 医学系研究科, 教授 (00221797)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: HBV / receptor / NTCP / restriction factor / HBV core / mouse hepatocyte / entry / マウス肝細胞 / 制限因子 / HBVコア抗原 / ウイルスentry / HBV感染受容体 / coreceptor / 抵抗（制限）因子 / 抑制因子

Outline of Final Research Achievements

HBV can not establish the infection in mouse liver cells expressing human NTCP, which is the most important molecule for HBV entry. Since an HBV producing vector transfection into mouse hepatocytes leads to HBV production, there should be some restriction factors to block HBV entry into the cells. In order to clarify the factors in terms of HBV core protein interacting factors, we have established an HBV core protein expressing mouse hepatocyte line.

Research Products

• [Journal Article] Full-length isoforms of KSHV LANA accumulate in the cytoplasm of cells undergoing the lytic cycle of replication. (2017)
  • Author(s): H. Jacques Garriguesa, Kellie Howarda, Serge Barcya , Minako Ikomaa , Ashlee V. 5 Mosesb , Gail H. Deutschc , David Wud , Keiji Ueda and Timothy M. Rose.
  • Journal Title: J. Virol. Volume: 91 Issue: 24
  • DOI: 10.1128/jvi.01532-17
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Restoring PU.1 induces apoptosis and modulates viral transactivation via interferon-stimulated genes in primary effusion lymphoma (2017)
  • Author(s): Hiroki Goto, Ryusho Kariya, Eriko Kudo, Yutaka Okuno, Keiji Ueda, Harutaka Katano and Seiji Okada.
  • Journal Title: Oncogene Volume: 138 Pages: 1-11
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Investigation of a novel hepatitis B virus surface antigen (HBsAg) escape mutant affecting immunogenicity. (2017)
  • Author(s): Hossain, Md. G., and Ueda, K.
  • Journal Title: PLOS ONE Volume: x Pages: 1-22
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A chimeric protein composed of NuMA fused to the DNA binding domain of LANA is sufficient for the ori-P-dependent DNA replication. (2017)
  • Author(s): Ohsaki, E., and Ueda, K.
  • Journal Title: Virology Volume: 500 Pages: 190-197
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Inhibitory effect of CDK9 inhibitor FIT-039 on hepatitis B virus propagation. (2016)
  • Author(s): Tomohisa Tanaka, Kaori Okuyama-Dobashi, Shuko Murakami, Wenjia Chen, Toru Okamoto, Keiji Ueda, Takamitsu Hosoya, Yoshiharu Matsuura, Akihide Ryo, Yasuhito Tanaka, Masatoshi Hagiwara, Kohji Moriishi.
  • Journal Title: Antiviral Research Volume: 133 Pages: 156-164
  • Peer Reviewed / Open Access
• [Presentation] Analysis of the HBV life cycle in a HepG2 expressing human NTCP. (2016)
  • Author(s): Retno Rahayu, Eriko Osaki, Toru Okamoto, Koichi Watashi, Keiji Ueda.
  • Organizer: 第64回日本ウイルス学会学術集会． 2016年10月23-25日．札幌．
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23
• [Presentation] CDK inhibitor FIT-039 suppresses HBV propagation. (2016)
  • Author(s): Kohji Moriishi, Tomohisa Tanaka, Kaori Okuyama-Dobashi,Wenjia Chen, Toru Okamoto, Keiji Ueda, Takamitsu Hosoya, Yoshiharu Matsuura, Akihide Ryo, Yasuhito Tanaka, Masatoshi Hagiwara.
  • Organizer: 第64回日本ウイルス学会学術集会． 2016年10月23-25日．札幌．
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-23
• [Book] B型肝炎ウイルスのウイルス学的特徴」 B型肝炎ウイルスの現状とワクチン定期接種化の意義 (2017)
  • Author(s): 34.上田啓次．
  • Total Pages: 160
  • Publisher: 医薬ジャーナル社