Research on mechanism of hepatitis E virus egress utilizing membrane traffic

• Project/Area Number: 25860343
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Jichi Medical University
• Principal Investigator: NAGASHIMA Shigeo 自治医科大学, 医学部, 講師 (60433116)
• Research Collaborator: OKAMOTO Hiroaki 自治医科大学, 医学部, 教授 (30177092) ; TAKAHASHI Masaharu 自治医科大学, 医学部, 講師 (70326841) ; NISHIZAWA Tsutomu 自治医科大学, 医学部, 非常勤講師 (30306112) ; KOBAYASHI Tominari 自治医科大学, 医学部, 助教 (00634164) ; YASHIRO Takashi 自治医科大学, 医学部, 教授 (80119859) ; KOUKI Tom 自治医科大学, 医学部, 客員研究員 (70350436)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: E型肝炎ウイルス / エクソソーム / 多胞体 / 出芽 / 放出 / エクソソーム分泌経路 / エンベロープ

Outline of Final Research Achievements

We investigated the requirement of the exosomal pathway for the release of hepatitis E virus (HEV) virions by using an inhibitor and accelerator of exosome release or small interfering RNAs against Rab27A and Hrs. These studies revealed that the exosomal pathway is required for the release of HEV virions. Electron microscopic observations revealed the presence of membrane-associated virus particles with a diameter of approximately 50 nm within the multivesicular body (MVB), which possessed internal vesicles in infected cells. These findings indicate that membrane-associated HEV particles are released together with internal vesicles (exosomes) through MVBs by the cellular exosomal pathway.

Research Products

• [Journal Article] Hepatitis E virus egress depends on the exosomal pathway, with secretory exosomes derived from multivesicular bodies (2014)
  • Author(s): Nagashima S, Jirintai S, Takahashi M, Kobayashi T, Tanggis, Nishizawa T, Kouki T, Yashiro T, Okamoto H
  • Journal Title: Journal of General Virology Volume: 95 Issue: 10 Pages: 2166-2175
  • DOI: 10.1099/vir.0.066910-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Rat hepatitis E virus derived from wild rats (Rattus rattus) propagates efficiently in human hepatoma cell lines (2014)
  • Author(s): Jirintai S, Tanggis, Mulyanto, Suparyatmo JB, Takahashi M, Kobayashi T, Nagashima S, Nishizawa T, Okamoto H
  • Journal Title: Virus Research Volume: 185 Pages: 92-102
  • DOI: 10.1016/j.virusres.2014.03.002
  • Peer Reviewed
• [Journal Article] Molecular characterization of a novel hepatitis E virus (HEV) strain obtained from a wild boar in Japan that is highly divergent from the previously recognized HEV strains (2014)
  • Author(s): Takahashi M, Nishizawa T, Nagashima S, Jirintai S, Kawakami M, Sonoda Y, Suzuki T, Yamamoto S, Shigemoto K, Ashida K, Sato Y, Okamoto H
  • Journal Title: Virus Research Volume: 180 Pages: 59-69
  • DOI: 10.1016/j.virusres.2013.12.014
  • Peer Reviewed
• [Journal Article] Marked genomic heterogeneity of rat hepatitis E virus strains in Indonesia demonstrated on a full-length genome analysis (2014)
  • Author(s): Mulyanto, Suparyatmo JB, Andayani IG, Khalid, Takahashi M, Ohnishi H, Jirintai S, Nagashima S, Nishizawa T, Okamoto H
  • Journal Title: Virus Research Volume: 179 Pages: 102-112
  • DOI: 10.1016/j.virusres.2013.10.029
  • Peer Reviewed
• [Journal Article] The membrane on the surface of hepatitis E virus particles is derived from the intracellular membrane and contains trans-Golgi network protein 2 (2014)
  • Author(s): Nagashima S, Takahashi M, Jirintai S, Tanggis, Kobayashi T, Nishizawa T, Okamoto H
  • Journal Title: Archives of Virology Volume: 159 Issue: 5 Pages: 979-991
  • DOI: 10.1007/s00705-013-1912-3
  • Peer Reviewed
• [Journal Article] Characterization of sporadic acute hepatitis E and comparison of hepatitis E virus genomes in acute hepatitis patients and pig liver sold as food in Mie, Japan (2014)
  • Author(s): Okano H, Takahashi M, Isono Y, Tanaka H, Nakano T, Oya Y, Sugimoto K, Ito K, Ohmori S, Maegawa T, Kobayashi M, Nagashima S, Nishizawa T, Okamoto H
  • Journal Title: Hepatology Research Volume: 印刷中 Issue: 10
  • DOI: 10.1111/hepr.12216
  • Peer Reviewed
• [Journal Article] strains isolated from an acute hepatitis patient and a wild boar in Mie, Japan (2013)
  • Journal Title: Hepatol Res Volume: 印刷中 Issue: 6 Pages: 694-699
  • DOI: 10.1111/hepr.12155
  • Peer Reviewed
• [Presentation] E型肝炎ウイルスの細胞侵入・放出機構の解明 (2015)
  • Author(s): 長嶋茂雄
  • Organizer: Liver Forum in Kyoto 第17回学術集会
  • Place of Presentation: 京都 （京都ホテルオークラ）
  • Year and Date: 2015-03-28
  • Invited
• [Presentation] E型肝炎ウイルスの細胞侵入機構の解析 (2014)
  • Author(s): 長嶋茂雄、吉林台、小林富成、唐吉思、高橋雅春、西澤勉、岡本宏明
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: 横浜 （パシフィコ横浜）
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] 細胞内膜輸送系を利用したE型肝炎ウイルスの放出機構の解析 (2013)
  • Author(s): 長嶋 茂雄、高橋 雅春、吉林台、小林 富成、西澤 勉、岡本 宏明
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸国際会議場
• [Remarks] 自治医科大学医学部 感染・免疫学講座 ウイルス学部門
  • URL: http://www.jichi.ac.jp/virology/
• [Remarks] 自治医科大学医学部 感染・免疫学講座 ウイルス学部門
  • URL: http://www.jichi.ac.jp/virology/