The study of attachment and entry mechanism of hepatitis E virus into hepatocyte

• Project/Area Number: 24790452
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: SHIOTA Tomoyuki 国立感染症研究所, その他部局等, 任期付研究員 (80616144)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: E型肝炎ウイルス(HEV) / HEV感受・非感受性細胞 / 網羅的遺伝子発現解析 / プロテオーム解析 / cDNAライブラリスクリーニング / レセプター候補 / 結合能 / 感染能 / E型肝炎ウイルス（HEV) / HEVレセプター候補 / HEV 非感受性細胞 / レセプター候補安定発現HEV非感受性細胞 / HEV高速増殖能獲得馴化細胞株 / HEV感染阻害評価系 / ペプチドモチーフ / 相互作用因子 / E型肝炎ウイルス（HEV）へのパンニング法の応用 / HEV感受性細胞cDNAライブラリ作製 / HEV感受・非感受性細胞の網羅的遺伝子発現解析 / HEV感受・非感受性細胞間の多様な遺伝子発現差 / E型肝炎ウイルス / 肝細胞 / 吸着 / 侵入 / 感受性細胞 / 非感受性細胞 / 感染性規定宿主因子

Outline of Final Research Achievements

Comparative analyses between hepatitis E virus (HEV) infection-permissive and -nonpermissive human hepatocytes by using gene expression profiling, proteome analysis and screening of cDNA library led to the identification of strong receptor candidate. We are now planning to elucidate the function of this candidate gene to viral attachment and entry into hepatocytes. To date, the effective method to control HEV infection is not yet established, but we believe this study will contribute to the development of effective vaccine and therapeutic drugs.

Research Products

• [Journal Article] Establishment of hepatitis E virus infection-permissive and -non-permissive human hepatoma PLC/PRF/5 subclones (2015)
  • Author(s): Tomoyuki Shiota, Tian-Cheng Li, Sayaka Yoshizaki, Takanobu Kato, Takaji Wakita and Koji Ishii
  • Journal Title: Microbiology and Immunology Volume: 59(2) Issue: 2 Pages: 89-94
  • DOI: 10.1111/1348-0421.12219
  • NAID: 40020388179
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Molecular detection of Hepatitis E virus in rivers in the Philippines (2014)
  • Author(s): Tian-Cheng Li, Tingting Yang, Tomoyuki Shiota, Sayaka Yoshizaki, Hiromu Yoshida, Mariko Saito, Toshifumi Imagawa, Fidelino F. Malbas, Socorro P. Lupisan, Hitoshi Oshitani, Takaji Wakita, and Koji Ishii
  • Journal Title: American Journal of Tropical Medicine & Hygiene Volume: 90(4) Issue: 4 Pages: 764-766
  • DOI: 10.4269/ajtmh.13-0562
  • Peer Reviewed / Open Access
• [Journal Article] The hepatitis E virus capsid C-terminal region is essential for the viral life cycle: implication for viral genome encapsidation and particle stabilization (2013)
  • Author(s): Shiota T, Li TC, Yoshizaki S, Kato T, Wakita T, Ishii K
  • Journal Title: J Virol. Volume: 87(10): Issue: 10 Pages: 6031-6036
  • DOI: 10.1128/jvi.00444-13
  • Peer Reviewed
• [Journal Article] The hepatitis e virus capsid C-terminal region is essential for the viral life cycle: implication for viral genome encapsidation and particle stabilization. (2013)
  • Author(s): Tomoyuki Shiota, Tiang-Cheng Li, Sayaka Yoshizaki, Takaji Wakita, and Koji Ishii.
  • Journal Title: Journal of Virology Volume: Epub ahead of print
  • Peer Reviewed
• [Presentation] E型肝炎ウイルス感染性規定宿主因子候補に関する研究 (2014)
  • Author(s): 塩田智之、李天成、吉崎佐矢香、西村順裕、清水博之、下島昌幸、西條政幸、脇田隆字、石井孝司
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜,神奈川
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] Searching for the host factors involved in hepatitis E virus infection (2014)
  • Author(s): Tomoyuki Shiota
  • Organizer: 2014 MGH-UTokyo Symposium: Frontiers in Biomedical Engineering (Celebrating the 10th year of MGH-UTokyo Summer Student Internship Program)
  • Place of Presentation: Simches Conference Room 3110, MGH, Boston, MA, USA
  • Year and Date: 2014-09-24
  • Invited
• [Presentation] E型肝炎ウイルス感染性規定宿主因子の探索に関する研究 (2013)
  • Author(s): 塩田智之, 李天成, 吉崎佐矢香, 西村順裕, 清水博之, 下島昌幸, 西條政幸, 脇田隆字, 石井孝司
  • Organizer: 第61回日本ウイルス学会学術集
  • Place of Presentation: 神戸国際会議場
• [Presentation] E型肝炎ウイルスレプリコンの構築とレプリコン包埋VLP作成の検討 (2013)
  • Author(s): 石井孝司, 李 天成, 吉崎佐矢香, 塩田智之, 脇田隆字
  • Organizer: 第61回日本ウイルス学会学術集
  • Place of Presentation: 神戸国際会議場
• [Presentation] Characterization of Hepatitis E Virus Capsid C-terminal 52 Amino Acids in the Viral Life-Cycle (2012)
  • Author(s): Tomoyuki Shiota, Tiang-Cheng Li, Sayaka Yoshizaki, Naokazu Takeda, Takaji Wakita, and Koji Ishii
  • Organizer: The 11th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 兵庫県淡路市
• [Presentation] Characterization of Hepatitis E Virus Capsid C-terminal 52 Amino Acids in the Viral Life-Cycle (2012)
  • Author(s): Tomoyuki Shiota, Tiang-Cheng Li, Sayaka Yoshizaki, Naokazu Takeda, Takaji Wakita, and Koji Ishii
  • Organizer: The 34th Naito Conference on Infection, Immunity and their Control for Health: Mucosal Barrier, Pathogen and Vaccine
  • Place of Presentation: 北海道札幌市
• [Presentation] E型肝炎ウイルス生活環におけるカプシド蛋白C末端52アミノ酸の機能解析 (2012)
  • Author(s): 塩田 智之, 李 天成, 吉崎 佐矢香, 武田 直和, 脇田 隆字, 石井 孝司
  • Organizer: 第60回 日本ウイルス学会
  • Place of Presentation: 大阪府大阪市