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Analysis of replication mechanism and pathogenesis of hepatitis E virus using infectious clone

Research Project

Project/Area Number 25460580
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Virology
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

ISHII Koji  国立感染症研究所, ウイルス第二部, 室長 (40280763)

Co-Investigator(Kenkyū-buntansha) Li Tian Cheng  国立感染症研究所, ウイルス第二部, 主任研究官 (90370957)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsE型肝炎ウイルス / 複製機構 / 感染メカニズム / 病原性 / レプリコン / プロテアーゼ
Outline of Final Research Achievements

We constructed infectious hepatitis E virus (HEV) clone from infected porcine liver and replaced the structural protein to reporter genes resulted in successful construction of HEV replicon. This replicon was used for the screening of the library of chemical compounds. We found some compounds that shared the same bioactivity. Although more detailed analysis is still needed to reveal the effect of these compounds to HEV replication, but these results would contribute to the analysis of the mechanism of HEV replication and pathogenesis.
We also analyzed the processing of HEV nonstructural protein (ORF1) that encodes viral proteins responsible for the replication of HEV. We expressed whole ORF1 and potential protease region by using wheat germ-based cell free expression system. Protease activity was detected from ORF1 protein, suggesting that this cell free expression system is useful for the analysis of the processing mechanism of HEV nonstructural protein.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (49 results)

All 2016 2015 2014 2013

All Journal Article (23 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 14 results,  Open Access: 4 results,  Acknowledgement Compliant: 3 results) Presentation (26 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results)

  • [Journal Article] A Case of Chronic Hepatitis E Infection in a Persistently Immunosuppressed Patient Unable to be Eliminated after Ribavirin Therapy.2016

    • Author(s)
      Miyoshi M., Kakinuma S., Tanabe Y., Ishii K., Li T.C., Wakita T,, Tsuura Y., Watanabe H., Asahina Y., Watanabe M. and Ikeda T.
    • Journal Title

      Internal Medicine

      Volume: in press

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ferret Hepatitis E Virus Infection Induces Acute Hepatitis and Persistent Infection in Ferrets2016

    • Author(s)
      Li Tiancheng, Yang T, Sayaka Yoshizaki, Kataoka M, Ami Y, Suzaki Y, Kishida N, Shirakura M, Imai M, Asanuma H, Takeda N, Wakita T
    • Journal Title

      Vet Microbiol

      Volume: 183 Pages: 30-36

    • DOI

      10.1016/j.vetmic.2015.11.014

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] A型肝炎ウイルス2016

    • Author(s)
      石井孝司
    • Journal Title

      臨床検査

      Volume: in press

    • Related Report
      2015 Annual Research Report
  • [Journal Article] The high prevalence of hepatitis E virus infection in wild boars in Ibaraki Prefecture, Japan2015

    • Author(s)
      Motoya T., Nagata N., Komori H., Doi I., Kurosawa M., Keta T., Sasaki N and Ishii K.
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 77 Issue: 12 Pages: 1705-1709

    • DOI

      10.1292/jvms.15-0173

    • NAID

      130005115323

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Seroepidemiological study of hepatitis B virus markers in Japan2015

    • Author(s)
      Kiyohara T., Ishii K., Sugiyama M., Mizokami M. and Wakita T.
    • Journal Title

      Vaccine

      Volume: 33 Issue: 45 Pages: 6037-6042

    • DOI

      10.1016/j.vaccine.2015.08.034

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epidemiology of domestically-aquired hepatitis E virus infection in Japan: assessment of the nationally reported surveillance data, 2007-2013.2015

    • Author(s)
      Kanayama A., Arima Y., Tamagishi T., Kinoshita H., Sunagawa T., Yahata Y., Matsui T., Ishii K., Wakita T. and Oishi K.
    • Journal Title

      Journal of Medical Microbiology

      Volume: 64 Issue: 7 Pages: 752-758

    • DOI

      10.1099/jmm.0.000084

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Generation of hepatitis E virus-like particles of two new genotypes G5 and G6 and comparison of antigenic properties with those of known genotypes2015

    • Author(s)
      Li T.C., Kataoka M., Takahashi K., Yoshizaki S., Kato T., Ishii K., Takeda N., Mishiro S. and Wakita T.
    • Journal Title

      Veterinary Microbiology

      Volume: 178 Issue: 1-2 Pages: 150-157

    • DOI

      10.1016/j.vetmic.2015.04.020

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epidemiological and genetic analysis of a 2014 outbreak of hepatitis A in Japan.2015

    • Author(s)
      Ishii K., Kiyohara T., Yoshizaki S., Kawabata K., Kanayama A., Yahata Y., Takahashi T., Kinoshita H., Saitou T., Sunagawa T., Oishi K., Uema M., Noda M. and Wakita T.
    • Journal Title

      Vaccine

      Volume: 33 Issue: 45 Pages: 6029-6036

    • DOI

      10.1016/j.vaccine.2015.04.061

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Construction and characterization of an infectious cDNA clone of rat hepatitis E virus.2015

    • Author(s)
      Li T.C., Yang T., Yoshizaki S., Ami Y., Suzaki Y., Ishii K., Haga K., Nakamura T., Ochiai S., Wakita T. and Johne R.
    • Journal Title

      Journal of General Virology

      Volume: 96 Issue: 6 Pages: 1320-1327

    • DOI

      10.1099/vir.0.000072

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Establishment of hepatitis E virus infection-permissive and -non-permissive human hepatoma PLC/PRF/5 subclones2015

    • 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

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A型肝炎の分子疫学的解析2015

    • Author(s)
      石井孝司
    • Journal Title

      肝胆膵

      Volume: 71 Pages: 983-989

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 生肉食とE型肝炎2015

    • Author(s)
      石井孝司、今川稔文
    • Journal Title

      日本臨床

      Volume: 73 Pages: 693-698

    • Related Report
      2015 Annual Research Report
  • [Journal Article] A型肝炎ウイルスのウイルス学的特徴2015

    • Author(s)
      石井孝司
    • Journal Title

      日本臨床

      Volume: 73 Pages: 576-583

    • Related Report
      2015 Annual Research Report
  • [Journal Article] A型肝炎ウイルス(HAV)の疫学2015

    • Author(s)
      鈴木哲朗、石井孝司
    • Journal Title

      日本臨床

      Volume: 73 Pages: 571-575

    • Related Report
      2015 Annual Research Report
  • [Journal Article] A型肝炎2015

    • Author(s)
      石井孝司
    • Journal Title

      救急医学

      Volume: 39 Pages: 1434-1437

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Molecular detection of Hepatitis E virus in rivers in the Philippines2014

    • 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

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chronic Hepatitis B Prevalence among Children and Mothers: Results from a Nationwide, Population-Based Survey in Lao People’s Democratic Republic.2014

    • Author(s)
      Xeuatvongsa A., Komada K., Kitamura T., Vongphrachanh P., Pathammavong C., Phounphenghak K., Sisouk T., Phonekeo D., Sengkeopaseuth B., Som-Oulay V., Ishii K., Wakita T., Sugiyama M. and Hachiya M.
    • Journal Title

      PLOS One

      Volume: 9 Issue: 2 Pages: e88829-e88829

    • DOI

      10.1371/journal.pone.0088829

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Suppression of La Antigen Exerts Potential Antiviral Effects against Hepatitis A Virus.2014

    • Author(s)
      Jiang X, Kanda T, Wu S, Nakamoto S, Saito K, Shirasawa H, Kiyohara T, Ishii K, Wakita T, Okamoto H, Yokosuka O.
    • Journal Title

      PLoS One.

      Volume: 9 Issue: 7 Pages: e101993-e101993

    • DOI

      10.1371/journal.pone.0101993

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 環境中A型肝炎ウイルス遺伝子の検出と分子疫学的応用2014

    • Author(s)
      石井孝司
    • Journal Title

      臨床とウイルス

      Volume: 42 Pages: 242-246

    • Related Report
      2014 Research-status Report
  • [Journal Article] A型肝炎ウイルス感染症2014

    • Author(s)
      石井孝司、清原知子、脇田隆字
    • Journal Title

      東京小児科医会報

      Volume: 33 Pages: 11-17

    • Related Report
      2014 Research-status Report
  • [Journal Article] A型肝炎、E型肝炎2014

    • Author(s)
      石井孝司
    • Journal Title

      臨床と微生物

      Volume: 41 Pages: 72-78

    • Related Report
      2014 Research-status Report
  • [Journal Article] Neutralizing antibodies induced by cell culture-derived hepatitis C virus protect against infection in mice.2013

    • Author(s)
      Akazawa D, Moriyama M, Yokokawa H, Omi N, Watanabe N, Date T, Morikawa K, Aizaki H, Ishii K, Kato T, Mochizuki H, Nakamura N, Wakita T.
    • Journal Title

      Gastroenterology

      Volume: 145 Issue: 2 Pages: 447-455

    • DOI

      10.1053/j.gastro.2013.05.007

    • Related Report
      2013 Research-status Report
    • 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 stabilization2013

    • 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

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Neutralizing antibody induction by vaccination of cell culture-generated hepatitis C virus particles in non-human primate model2015

    • Author(s)
      1.Yokokawa H., Higashino A., Suzuki S., Suzuki T., Akari H., Kato T., Ishii K. and Wakita T.
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会合同大会
    • Place of Presentation
      神戸市
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] A reverse genetic system to explore the function of rat hepatitis E virus ORF42015

    • Author(s)
      Li T.C., Yang T., Ami Y., Suzaki Y., Yoshizaki S., Ishii K., Haga K., Nakamura T., Ochiai S., Takeda N.. Johne R. and Wakita T.
    • Organizer
      第63回日本ウイルス学会
    • Place of Presentation
      福岡市
    • Year and Date
      2015-11-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] The validation study of hepatitis E virus receptor candidate2015

    • Author(s)
      Shiota T., Li T.C., Yoshizaki S., Nishimura Y., Shimizu H., Shimojima M., Saijo M., Wakita T. and Ishii K.
    • Organizer
      第63回日本ウイルス学会
    • Place of Presentation
      福岡市
    • Year and Date
      2015-11-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] Immunogenicity of Booster Vaccination with an Aluminum-absorbed Hepatitis A Vaccine after Primary Immunization with Aluminum-free Japanese Hepatitis A Vaccine2015

    • Author(s)
      Fukushima S., Nakano T., Kiyohara T., Ishii K. and Hamada A.
    • Organizer
      9th Vaccine & ISV Congress
    • Place of Presentation
      Seoul, Republic Of Korea
    • Year and Date
      2015-10-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A型肝炎ワクチン(エイムゲン®とHAVRIX®)の互換性に関する研究2015

    • Author(s)
      福島慎二、清原知子、石井孝司、中野貴司、濱田篤郎
    • Organizer
      第18回日本渡航医学会学術集会
    • Place of Presentation
      名古屋市
    • Year and Date
      2015-07-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] 本邦におけるB型肝炎流行状況の調査2015

    • Author(s)
      清原知子、石井孝司、脇田隆字
    • Organizer
      第51回日本肝臓学会総会
    • Place of Presentation
      熊本市
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 日本におけるA型肝炎の現状について2015

    • Author(s)
      石井孝司
    • Organizer
      第11回日本小児消化管感染症研究会
    • Place of Presentation
      大阪市
    • Year and Date
      2015-02-07
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] A型肝炎の家族内感染についての疫学的解析(2014年上半期を中心に)2014

    • Author(s)
      河端邦夫、清原知子、石井孝司、脇田隆字、金山敦宏、八幡裕一郎、松井珠乃、砂川富正、大石和徳
    • Organizer
      第18回日本ワクチン学会
    • Place of Presentation
      福岡市
    • Year and Date
      2014-12-06 – 2014-12-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 不活化A型肝炎ワクチンの互換性研究~エイムゲンとHAVRIX~2014

    • Author(s)
      福島慎二、清原知子、石井孝司、中野貴司、濱田篤郎
    • Organizer
      第18回日本ワクチン学会
    • Place of Presentation
      福岡市
    • Year and Date
      2014-12-06 – 2014-12-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 10-15歳児におけるHBs抗原保有率調査2014

    • Author(s)
      清原知子、石井孝司、杉山真也、溝上雅史、脇田隆字
    • Organizer
      第18回日本ワクチン学会
    • Place of Presentation
      福岡市
    • Year and Date
      2014-12-06 – 2014-12-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 培養細胞由来HAV粒子のマーモセットにおける抗HCV抗体誘導能の検討2014

    • Author(s)
      横川 寛、中村紀子、東濃篤徳、鈴木紗織、明里宏文、加藤孝宣、石井孝司、脇田隆字
    • Organizer
      第62回日本ウイルス学会
    • Place of Presentation
      横浜市
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Research-status Report
  • [Presentation] 2014年春季に日本で多発したA型肝炎の分子疫学的解析2014

    • Author(s)
      石井孝司、清原知子、吉崎佐矢香、八幡裕一郎、河端邦夫、金山敦宏、山岸拓也、高橋琢理、有馬雄三、木下一美、齊藤剛仁、松井珠乃、大石和徳、砂川富正、脇田隆字
    • Organizer
      第62回日本ウイルス学会
    • Place of Presentation
      横浜市
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Research-status Report
  • [Presentation] E型肝炎ウイルス感染性規定因子宿主候補に関する研究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
    • Place of Presentation
      横浜市
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Research-status Report
  • [Presentation] 日本におけるA型肝炎の現状について2014

    • Author(s)
      石井孝司
    • Organizer
      第29回関東甲信静支部ウイルス研究部会
    • Place of Presentation
      長野市
    • Year and Date
      2014-09-25 – 2014-09-26
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Epidemiological and genetic analysis of an outbreak of hepatitis A in Japan, 2014.2014

    • Author(s)
      Ishii K.
    • Organizer
      The 11th Japan-Taiwan Symposium on New Technologies Applied to Public Health Including Foodborne Diseases and Drug Resistance.
    • Place of Presentation
      台北、台湾
    • Year and Date
      2014-09-11 – 2014-09-12
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Epidemiological and genetic analysis of a large outbreak of hepatitis A in Japan, 2014.2014

    • Author(s)
      Ishii K.
    • Organizer
      The 10th China-Japan International Conference of Virology
    • Place of Presentation
      長春、中国
    • Year and Date
      2014-08-25 – 2014-08-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Molecular epidemiological analysis of recent hepatitis A in Japan and Asian countries.2014

    • Author(s)
      Ishii K. Kiyohara T., Yoshizaki S., Shimada T., Nakamura N., Nakashima K., Tada Y., Noda M., Wakita T.
    • Organizer
      10th Asia Pacific Travel Health Conference
    • Place of Presentation
      Ho Chi Minh City, Viet Nam
    • Year and Date
      2014-05-07 – 2014-05-11
    • Related Report
      2014 Research-status Report
  • [Presentation] Characterization of a case of hepatitis E that imported from Spain.2014

    • Author(s)
      Li TC., Ochiai K., Yang T., Yoshizaki S., Takeda N., Ishii K., Wakita T.
    • Organizer
      10th Asia Pacific Travel Health Conference
    • Place of Presentation
      Ho Chi Minh City, Viet Nam
    • Year and Date
      2014-05-07 – 2014-05-11
    • Related Report
      2014 Research-status Report
  • [Presentation] Epidemiological and genetic analysis of hepatitis A in Japan.2014

    • Author(s)
      Ishii K., Kiyohara T., Yoshizaki S., Tada T., Shimada T., Nakashima K., Noda M., Wakita T.
    • Organizer
      18th International Picornavirus Symposium
    • Place of Presentation
      Blankenberge, Belgium
    • Related Report
      2013 Research-status Report
  • [Presentation] Induction of neutralizing antibodies by vaccination with cell culture derived hepatitis C virus particles in primate model.2013

    • Author(s)
      Yokokawa H., Moriyama M., Nakamura N., Higashino A., Akari H., Kato T., Ishii K. and Wakita T.
    • Organizer
      20th International Meeting on HCV and Related Viruses
    • Place of Presentation
      Melbourne, Australia
    • Related Report
      2013 Research-status Report
  • [Presentation] ワクシニアウイルスDIs株を母体としたインフルエンザHA組換えワクチンの混合接種によるカニクイザルでの発症予防効果2013

    • Author(s)
      宗片圭祐、安井文彦、伊藤 靖、石井孝司、七戸新太郎、喜田 宏、小笠原一誠、小原道法
    • Organizer
      第17回日本ワクチン学会
    • Place of Presentation
      津
    • Related Report
      2013 Research-status Report
  • [Presentation] A型肝炎のリスクアセスメント2013

    • Author(s)
      清原知子、石井孝司、多田有希、脇田隆字
    • Organizer
      第17回日本ワクチン学会
    • Place of Presentation
      津
    • Related Report
      2013 Research-status Report
  • [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
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [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
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] 結晶構造解析とQM/MM計算の組み合わせによるノロウイルスとルイス抗原の結合解析2013

    • Author(s)
      白土東子、石田豊和、熊谷安希子、伊藤浩美、古川早苗、染谷雄一、石井孝司、脇田隆字、成松 久、久保田智己
    • Organizer
      第61回日本ウイルス学会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] 小児におけるHBs抗原保有率調査2013

    • Author(s)
      清原知子、石井孝司、杉山真也、溝上雅史、脇田隆字
    • Organizer
      第61回日本ウイルス学会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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