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Identification of the budding site of hepatitis B virus infectious particles (Dane particles)

Research Project

Project/Area Number 18K08004
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionKonan Women's University

Principal Investigator

Hotta Haku  甲南女子大学, 医療栄養学部, 教授 (40116249)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsB型肝炎ウイルス(HBV) / 感染性粒子(Dane粒子) / エンベロープリン脂質 / 出芽・放出部位 / 小胞体(ER) / 多胞体(MVB) / エクソソーム / 電子顕微鏡 / 出芽部位 / 細胞外放出 / 酵素親和性 / 多小胞体(MVB) / B型肝炎ウイルス / 感染性粒子(Dane粒子) / 小胞体(ER) / 多小胞体(MVB)
Outline of Final Research Achievements

We investigated the possible budding site(s) of the hepatitis B virus (HBV) virions as well as their release from the infected cells and the transmission to the uninfected target cells by means of their phospholipase A2 susceptibility, virion density, electron microscopic observations, knockdown experiments of the molecules involved in the functions of the endoplasmic reticulum (ER) and multivesicular body (MVB), and the exosome. We also performed comparative analyses between HBV and hepatitis C virus (HCV) as well as HBV and hepatitis D virus (HDV). Our results clearly demonstrated that the viral envelope properties differed between HBV and HCV, and that the uncoating process of the viral particles differed between HBV and HDV. Our results also suggested that the exosome pathway is involved in the release and transmission of HBV infectivity from the infected cells to the uninfected target cells. The precise determination of the HBV budding site(s) remains to be investigated.

Academic Significance and Societal Importance of the Research Achievements

B型肝炎ウイルス(HBV)とC型肝炎ウイルス(HCV)の感染性は、ある種のホスホリパーゼA2により非常に効率よく中和されるが、中和の機序は、HCVではエンベロープ破壊であるのに対して、HBVでは脱殻阻害であり、両ウイルスで明らかに異なることを実証した。また、HBVとD型肝炎ウイルス(HDV)は同じエンベロープを有しているが、細胞内侵入後の脱殻の過程が、両ウイルスで明らかに異なることを実証した。さらに、HBV感染細胞からの感染伝播に、HBV粒子やHBVゲノムを包含するエクソソームが関与することを実証した。これらの研究成果は、HBVのウイルス学的性質を明らかにするうえで重要なものと考えられる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (25 results)

All 2021 2020 2019 2018

All Journal Article (9 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 9 results,  Open Access: 6 results) Presentation (16 results) (of which Int'l Joint Research: 8 results,  Invited: 1 results)

  • [Journal Article] Identification of an antiviral component from the venom of the scorpion Liocheles australasiae using transcriptomic and mass spectrometric analyses2021

    • Author(s)
      Miyashita Masahiro、Mitani Naoya、Kitanaka Atsushi、Yakio Mao、Chen Ming、Nishimoto Sachiko、Uchiyama Hironobu、Sue Masayuki、Hotta Hak、Nakagawa Yoshiaki、Miyagawa Hisashi
    • Journal Title

      Toxicon

      Volume: 191 Pages: 25-37

    • DOI

      10.1016/j.toxicon.2020.12.007

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potent virucidal activity of honeybee "Apis mellifera" venom against hepatitis C virus2020

    • Author(s)
      Sarhan M, El-Bitar AMH, Hotta H.
    • Journal Title

      Toxicon

      Volume: 188 Pages: 55-64

    • DOI

      10.1016/j.toxicon.2020.10.014

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prevalence and genotype distribution of hepatitis B virus among migrant workers in Lombok Island, Indonesia2020

    • Author(s)
      Yamani LN, Triani E, Amin M, Juniastuti, Utsumi T, Soetjipto, Nasronudin, Yano Y, Hotta H, Hayashi Y, Lusida MI.
    • Journal Title

      Asian Pacific Journal of Tropical Medicine

      Volume: 13 Pages: 8-16

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] revalence and genotype distribution of hepatitis B virus among migrant workers in Lombok Island, Indonesia2020

    • Author(s)
      2.Yamani LN, Triani E, Amin M, Juniastuti, Utsumi T, Soetjipto, Nasronudin, Yano Y, Hotta H, Hayashi Y, Lusida MI
    • Journal Title

      Asian Pacific Journal of Tropical Medicine

      Volume: 13 Issue: 1 Pages: 8-16

    • DOI

      10.4103/1995-7645.273568

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Smp76, a scorpine like-peptide isolated from the venom of the scorpion Scorpio maurus palmatus, with a potent antiviral activity against hepatitis C virus and dengue virus2019

    • Author(s)
      1.El-Bitar AMH, Sarahan M, Abdel-Rahman MA, Quintero-Hernandez V, Aoki-Utsubo C, Moustafa MA, POssani LD, Hotta H
    • Journal Title

      International Journal of Peptide Research and Therapeutics

      Volume: None (0nline) Issue: 2 Pages: 811-821

    • DOI

      10.1007/s10989-019-09888-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Peroxiredoxin 1, a novel HBx-interacting protein, interacts with exsome component 5 and negatively regulates hepatitis B virus (HBV) propagation through degradation of HBV RNA.2019

    • Author(s)
      Lin Deng, Xiang Gan, Masahiko Ito, Ming Chen, Hussein H. Aly, Chieko Matsui, Takayuki Abe, Koichi Watashi,Takaji Wakita, Tetsuro Suzuki, Toru Okamoto, Yoshiharu Matsuura, Masashi Mizokami, Ikuo Shoji, and Hak Hotta.
    • Journal Title

      J. Virol

      Volume: 93 Issue: 6

    • DOI

      10.1128/jvi.02203-18

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Antiviral activities of Curcuma genus against hepatitis C virus2018

    • Author(s)
      Wahyuni TS, Permatasari AA, Widiandani T, Fuad A, Widyawaruyanti A, Aoki-Utsubo C, Hotta H
    • Journal Title

      Natural Product Communications

      Volume: 13 Pages: 1579-1582

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Virucidal and neutralizing activity tests for antiviral substances and antibodies2018

    • Author(s)
      Aoki-Utsubo C, Chen M, Hotta H
    • Journal Title

      Bio-protocol

      Volume: 8 Issue: 10

    • DOI

      10.21769/bioprotoc.2855

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Time-of-addition and temperature-shift assays to determine particular step(s) in the viral life cycle that is blocked by antiviral substance(s)2018

    • Author(s)
      Aoki-Utsubo C, Chen M, Hotta H
    • Journal Title

      Bio-protocol

      Volume: 8 Issue: 9

    • DOI

      10.21769/bioprotoc.2830

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] アメントフラボンのB型肝炎ウイルス、C型肝炎ウイルス感染阻害活性について2021

    • Author(s)
      靱千恵、亀岡正典、Jamilah Abbas、Muhammad Hanafi、堀田博
    • Organizer
      日本薬学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] センソ及びゴオウの抗デングウイルス活性に関する研究2021

    • Author(s)
      増井涼、杉本智潮、清水康晴、須藤慶一、渕野裕之、村瀬明香、河上仁美、川原信夫、西本幸子、堀田博
    • Organizer
      日本薬学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Venomics approach for identification of bioactive peptides from scorpion venom2020

    • Author(s)
      Miyashita M, Mitani N, Kitanaka A, Yakio M, Chen M, Nishimoto S, Hotta H, Nakagawa Y, Miyagawa H.
    • Organizer
      Asia Oceania Mass Spectrometry Conference
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヤエヤマサソリ毒液に含まれる抗ウイルス活性成分の単離・同定2020

    • Author(s)
      宮下正弘、三谷直也、北中淳史、焼尾真緒、陳明、西本幸子、堀田博、中川好秋、宮川恒
    • Organizer
      日本農芸化学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 5.Venomics approach for identification of bioactive peptides from scorpion venom2020

    • Author(s)
      Miyashita M, Mitani N, Kitanaka A, Yakio M, Chen M, Nishimoto S, Hotta H, Nakagawa Y, Miyagawa H
    • Organizer
      Asia-Oceania Mass Spectrometry Conference
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 1.Peroxiredoxin 1, a novel HBx-interacting protein, interacts with Exosc5 and negatively regulates HBV propagation through degradation of HBV RNA2019

    • Author(s)
      Deng L, Hotta H, Shoji I
    • Organizer
      The 7th Japan-Taiwan-Korea HBV Research Symposium
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 2.Further analysis of possible antiviral activity of CM-II-sPLA2 against HBV, HCV and HDV2019

    • Author(s)
      Hotta H, Aoki-Utsubo C, Chen M, Nishimoto S, Deng L, Miyayama Y, Hijikata M, Shindo K, Noda T, Kohara M, Tsukuda S, Watashi K, Wakita T
    • Organizer
      The 2019 International HBV Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 3.Identification of antimicrobial components from the venom of the scorpion Liocheles australasiae using an integrated mass spectrometric and transcriptomic approach2019

    • Author(s)
      Miyashita M, Mitani N, Kitanaka A, Yakio M, Chen M, Nishimoto S, Hotta H, Nakagawa Y, Miyagawa H
    • Organizer
      The 20th World Congress of the International Society on Toxinology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 4.Potent anti-HCV activity of bufalin and gamabufotalin obtained from dried toad cake2019

    • Author(s)
      Hotta, H, Aoki-Utsubo C, Nishimoto S, Fuchino H, Kawahara N, Masui R, Sugimoto C, Shimizu Y, Sudo K
    • Organizer
      The 26 th International Symposium on Hepatitis C virus and Related Viruses
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] インドネシア原産薬用植物の抗B型肝炎ウイルス活性について2019

    • Author(s)
      靱千恵,Puguh Indrasetiawan,Yan Mardian,Muhammad Hanafi,Sri Hartati,Tutik Sri Wahyuni,亀岡正典,矢野嘉彦,堀田博,林祥剛
    • Organizer
      日本生薬学会第66回年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 7.A chlorophyll derivative, methyl-pheophorbide A inhibits hepatitis C virus assembly by affecting apolipoprotein production2019

    • Author(s)
      Aoki-Utsubo C, Hotta H
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 8.Antiviral activity of steroidal cardiac glycosides obtained from dried toad cake against hepatitis C virus2019

    • Author(s)
      Hotta, H, Aoki-Utsubo C, Nishimoto S, Fuchino H, Kawahara N, Masui R, Sugimoto C, Shimizu Y, Sudo K
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Comparative analysis of antiviral activity of sPLA2 against HBV and HCV2018

    • Author(s)
      Hotta H, Chen M, Aoki-Utsubo C, Deng L, Miyayama Y, Hijikata M, Shindo K, Noda T, Kohara M, Watashi K, Wakita T
    • Organizer
      2018 International HBV Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Broad-spectrum antivirals that target viral envelope lipid bilayers2018

    • Author(s)
      Hotta H
    • Organizer
      Bromo Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Effect of antiviral activity of sPLA2 against HBV and HCV2018

    • Author(s)
      Miyayama Y, Chen M, Aoki-Utsubo C, Deng L, Shindo K, Noda T, Kohara M, Watashi K, Wakita T, Hijikata M, Hotta H
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 4.A crude extract from Cananga odorata exhibits antiviral activity against hepatitis B virus2018

    • Author(s)
      Indrasetiawan P, Aoki-Utsubo C, Hanafi M, Hartati S, Kameoka M, Hotta H, Hayashi Y
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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