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Characterization of HBV infection mediated by extracellular vesicles

Research Project

Project/Area Number 17K15709
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Virology
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

SANADA Takahiro  公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 研究員 (60721272)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsHBV / エキソソーム / ウイルス / B型肝炎ウイルス
Outline of Final Research Achievements

We investigated the extracellular vesicle (EV)-mediated transmission of hepatitis B virus (HBV) infection. Purified EVs from sera of HBV-infected chimeric mice with human liver contain viral DNA and to be capable or transmitting HBV DNA to naive hepatocytes. These HBV-DNA transmitting EVs were resistant to antibody neutralization. To establish a protective vaccine which can block HBV infection via EVs, we evaluated the effects of intranasal vaccination with HBs and HBc. Intranasal immunization with HBs-L and HBc formulated with CVP strongly induced cellular and humoral immune responses.

Academic Significance and Societal Importance of the Research Achievements

本研究により、エキソソームがHBVの産生機構および感染機構に関与していることが示唆された。本研究をさらに進めていくことで、現在問題となっているワクチン接種者でのHBV感染のメカニズムの解明につながっていくものと考えられる。また細胞性免疫を効率的に誘導できる免疫法に関して、基礎的なデータを得ることができた。本研究によって得られたデータは、エキソソームを介した感染を防御できる予防法の構築につながるものと考えられる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (17 results)

All 2019 2018 2017 Other

All Journal Article (6 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (7 results) (of which Int'l Joint Research: 5 results) Remarks (1 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Intranasal vaccination with HBs and HBc protein combined with carboxyl vinyl polymer induces strong neutralizing antibody, anti-HBs IgA, and IFNG response2019

    • Author(s)
      Sanada Takahiro、Yamamoto Naoki、Kayesh Mohammad Enamul Hoque、Tsukiyama-Kohara Kyoko、Hasegawa Hideki、Miyazaki Takashi、Takano Jun-ichiro、Shiogama Yumiko、Yasutomi Yasuhiro、Goh Yasumasa、Yoshida Osamu、Hiasa Yoichi、Kohara Michinori
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 520 Issue: 1 Pages: 86-92

    • DOI

      10.1016/j.bbrc.2019.09.072

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Construction of complete Tupaia belangeri transcriptome database by whole-genome and comprehensive RNA sequencing2019

    • Author(s)
      Sanada Takahiro、Tsukiyama-Kohara Kyoko、Shin-I Tadasu、Yamamoto Naoki、Kayesh Mohammad Enamul Hoque、Yamane Daisuke、Takano Jun-ichiro、Shiogama Yumiko、Yasutomi Yasuhiro、Ikeo Kazuho、Gojobori Takashi、Mizokami Masashi、Kohara Michinori
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 12372-12372

    • DOI

      10.1038/s41598-019-48867-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Avian H5N1 influenza virus infection causes severe pneumonia in the Northern tree shrew (Tupaia belangeri)2019

    • Author(s)
      Takahiro Sanada, Fumihiko Yasui, Tomoko Honda, Mohammad Enamul Hoque Kayesh, Jun-ichiro Takano, Yumiko Shiogama, Yasuhiro Yasutomi, Kyoko Tsukiyama-Kohara, and Michinori Kohara
    • Journal Title

      Virology

      Volume: 529 Pages: 101-110

    • DOI

      10.1016/j.virol.2019.01.015

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oxidative Stress and Immune Responses During Hepatitis C Virus Infection in Tupaia belangeri2017

    • Author(s)
      Kayesh Mohammad Enamul Hoque、Ezzikouri Sayeh、Sanada Takahiro、Chi Haiying、Hayashi Yukiko、Rebbani Khadija、Kitab Bouchra、Matsuu Aya、Miyoshi Noriaki、Hishima Tsunekazu、Kohara Michinori、Tsukiyama-Kohara Kyoko
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 9848-9848

    • DOI

      10.1038/s41598-017-10329-7

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Interferon-β response is impaired by hepatitis B virus infection in Tupaia belangeri2017

    • Author(s)
      Kayesh MEH, Ezzikouri S, Chi H, Sanada T, Yamamoto N, Kitab B, Haraguchi T, Matsuyama R, Nkogue CN, Hatai H, Miyoshi N, Murakami S, Tanaka Y, Takano JI, Shiogama Y, Yasutomi Y, Kohara M, Tsukiyama-Kohara K
    • Journal Title

      Virus Research

      Volume: 237 Pages: 47-57

    • DOI

      10.1016/j.virusres.2017.05.013

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Susceptibility and initial immune response of Tupaia belangeri cells to dengue virus infection2017

    • Author(s)
      Kayesh MEH, Kitab B, Sanada T, Hayasaka D, Morita K, Kohara M, *Tsukiyama-Kohara K.
    • Journal Title

      Infect Genet Evol.

      Volume: 51 Pages: 203-210

    • DOI

      10.1016/j.meegid.2017.04.003

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] HBs-large hybrid protein vaccination via intranasal route with carboxyl vinyl polymer rapidly induced strong neutralizing antibody and anti-HBs IgA.2019

    • Author(s)
      Sanada T, Kayesh MEH, Tsukiyama-Kohara K, Hasegawa H, Goh Y, Miyazaki T, Kohara M.
    • Organizer
      2019 AASLD THE LIVER MEETING.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Construction of genomic and transcriptomic database of the tree shrew (Tupaia belangeri), which is a small animal model of HBV infection.2019

    • Author(s)
      Sanada T, Tsukiyama-Kohara K, Shin-I T, Yamamoto N, Kayesh MEH, Kohara M.
    • Organizer
      2019 International HBV Meeting: The Molecular Biology of Hepatitis B Viruses.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Construction of genomic and transcriptomic database of the tree shrew (Tupaia belangeri), which is a small animal model of HBV infection.2019

    • Author(s)
      Sanada T, Tsukiyama-Kohara K, Shin-I T, Yamamoto N, Kayesh MEH, Kohara M.
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] HBs-large protein vaccination via intranasal route with carboxyl vinyl polymer induces strong neutralizing antibody and anti-HBs IgA2018

    • Author(s)
      SanadaT, Kayesh MEH, Chi H, Yamamoto N, Tsukiyama-Kohara K, Yoshida O, Hiasa Y, Hasegawa H, Sugiyama M, Mizokami M, Oda Y, Goh Y, Miyazaki T, Kamishita T, Kohara M.
    • Organizer
      2018 International HBV Meeting: The Molecular Biology of Hepatitis B Viruses
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] HBs-large protein vaccination via intranasal route with carboxyl vinyl polymer induces strong neutralizing antibody and anti-HBs IgA2018

    • Author(s)
      SanadaT, Kayesh MEH, Chi H, Yamamoto N, Tsukiyama-Kohara K, Yoshida O, Hiasa Y, Hasegawa H, Sugiyama M, Mizokami M, Oda Y, Goh Y, Miyazaki T, Kamishita T, Kohara M.
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Transmission of HBV mediated by extracellular vesicles2017

    • Author(s)
      Sanada T, Hirata Y, Naito Y, Yamamoto N, Kikkawa Y, Ishida Y, Yamasaki C, Tateno C, Ochiya T, Kohara M.
    • Organizer
      2017 International HBV Meeting: The Molecular Biology of Hepatitis B Viruses
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Transmission of HBV genomic DNA mediated by extracellular vesicles2017

    • Author(s)
      Sanada T, Hirata Y, Naito Y, Yamamoto N, Kikkawa Y, Ishida Y, Yamasaki C, Tateno C, Ochiya T, Kohara M.
    • Organizer
      XVII International Congress of Virology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Remarks] 公益財団法人 東京都医学総合研究所 感染制御プロジェクト

    • URL

      http://www.igakuken.or.jp/infectious/index.html

    • Related Report
      2019 Annual Research Report 2018 Research-status Report 2017 Research-status Report
  • [Patent(Industrial Property Rights)] B型肝炎ウイルスの複製阻害組成物2018

    • Inventor(s)
      棟方翼、小原道法、真田崇弘
    • Industrial Property Rights Holder
      公益財団法人 東京都医学総合研究所
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] B型肝炎ワクチン2017

    • Inventor(s)
      日浅陽一、小原恭子、小原道法、真田崇弘、郷保正、織田康則
    • Industrial Property Rights Holder
      日浅陽一、小原恭子、小原道法、真田崇弘、郷保正、織田康則
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 経鼻B型肝炎ワクチン組成物およびその製造方法2017

    • Inventor(s)
      上下泰造、宮崎隆、小原道法、真田崇弘、日浅陽一、吉田理他
    • Industrial Property Rights Holder
      上下泰造、宮崎隆、小原道法、真田崇弘、日浅陽一、吉田理他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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