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Empirical study on the formation of AIDS pathogenesis by primate model

Research Project

Project/Area Number 16H04682
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionKyoto University

Principal Investigator

MIURA Tomoyuki  京都大学, ウイルス・再生医科学研究所, 准教授 (40202337)

Co-Investigator(Renkei-kenkyūsha) IWAMI Shingo  九州大学, 理学研究院, 准教授 (90518119)
Research Collaborator KAWAKAMI Akihiko  
MATSUURA Kanako  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2018: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2016: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
KeywordsHIV / SHIV / アカゲザル / 動物モデル / 感染症 / エイズ
Outline of Final Research Achievements

Highly pathogenic SHIV was inoculated into rhesus macaques, and antiviral agents were administered to acute and chronic monkeys, respectively, and the attenuation of the amount of virus in blood observed with blocking new infections was measured. From the results obtained, the half-life of infected lymphocytes and infected macrophages was calculated by mathematical model analysis. Based on this information, the amount of macrophage-derived virus in the total amount of virus in the body was estimated. We have clarified the antiviral effect of current antiviral drugs on infected macrophages at individual level. It was examined histochemically whether macrophages function as virus reservoirs under antiviral therapy.

Academic Significance and Societal Importance of the Research Achievements

抗HIV薬の開発の過程ではウイルスのリンパ球への感染の阻止が指標として用いられており、マクロファージへの感染阻止および感染マクロファージへの抗ウイルス効果等はこれまでに検索されていない。このように個体レベルで未だ誰も検討していない問題に注目した点が独創的である。本研究計画が解明したHIV感染症におけるマクロファージ感染の意義は、実際の感染個体で得られる知見であるため、現行のヒトの多剤併用療法下で顕在化した諸問題へのマクロファージの関与を考えるうえで直接的かつ重要な基盤的情報となるものと考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (27 results)

All 2019 2018 2017 2016

All Journal Article (13 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 12 results,  Open Access: 12 results,  Acknowledgement Compliant: 2 results) Presentation (14 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Induction of neutralizing antibodies against tier 2 human immunodeficiency virus 1 in rhesus macaques infected with tier 1B simian/human immunodeficiency virus2019

    • Author(s)
      Himeno Ai、Ishida Yuki、Mori Hiromi、Matsuura Kanako、Kikukawa Minako、Sakawaki Hiromi、Miura Tomoyuki
    • Journal Title

      Archives of Virology

      Volume: 164 Issue: 5 Pages: 1297-1308

    • DOI

      10.1007/s00705-019-04173-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Experimental infection of Japanese macaques with simian retrovirus 52019

    • Author(s)
      Koide Rie、Yoshikawa Rokusuke、Okamoto Munehiro、Sakaguchi Shoichi、Suzuki Juri、Isa Tadashi、Nakagawa So、Sakawaki Hiromi、Miura Tomoyuki、Miyazawa Takayuki
    • Journal Title

      Journal of General Virology

      Volume: 100 Issue: 2 Pages: 266-277

    • DOI

      10.1099/jgv.0.001199

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of Macaca radiata as a non-human primate model of Dengue virus infection.2018

    • Author(s)
      Kato Fumihiro, Ishida Yuki, Kawakami Akihiko, Takasaki Tomohiko, Saijo Masayuki, Miura Tomoyuki, Hishiki Takayuki.
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 3421-3421

    • DOI

      10.1038/s41598-018-21582-9

    • NAID

      120006523833

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CXCR4- and CCR5-tropic HIV-1 clones are both tractable to grow in rhesus macaques.2018

    • Author(s)
      Doi N, Miura T, Mori H, Sakawaki H, Koma T, Adachi A, and Nomaguchi M.
    • Journal Title

      Frontiers in Microbiology

      Volume: 9 Pages: 2510-2510

    • DOI

      10.3389/fmicb.2018.02510

    • NAID

      120006937677

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Duration of SHIV production by infected cells is not exponentially distributed: Implications for estimates of infection parameters and antiviral efficacy2017

    • Author(s)
      CA. Beauchemin, T. Miura, S. Iwami
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 42765-42765

    • DOI

      10.1038/srep42765

    • NAID

      120005997746

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A highly pathogenic simian/human immunodeficiency virus effectively produces infectious virions compared with a less pathogenic virus in cell culture2017

    • Author(s)
      Iwanami S, Kakizoe Y, Morita S, Miura T, Nakaoka S, Iwami S
    • Journal Title

      Theor Biol Med Model

      Volume: 14 Issue: 1 Pages: 9-9

    • DOI

      10.1186/s12976-017-0055-8

    • NAID

      120006305768

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo virulence of MHC-adapted AIDS virus serially-passaged through MHC-mismatched hosts2017

    • Author(s)
      Seki Sayuri、Nomura Takushi、Nishizawa Masako、Yamamoto Hiroyuki、Ishii Hiroshi、Matsuoka Saori、Shiino Teiichiro、Sato Hironori、Mizuta Kazuta、Sakawaki Hiromi、Miura Tomoyuki、Naruse Taeko K.、Kimura Akinori、Matano Tetsuro
    • Journal Title

      PLOS Pathogens

      Volume: 13 Issue: 9 Pages: e1006638-e1006638

    • DOI

      10.1371/journal.ppat.1006638

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hirsutine, an Indole Alkaloid of Uncaria rhynchophylla, Inhibits Late Step in Dengue Virus Lifecycle2017

    • Author(s)
      Hishiki Takayuki、Kato Fumihiro、Tajima Shigeru、Toume Kazufumi、Umezaki Masahito、Takasaki Tomohiko、Miura Tomoyuki
    • Journal Title

      Frontiers in Microbiology

      Volume: 8 Pages: 1674-1674

    • DOI

      10.3389/fmicb.2017.01674

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A highly pathogenic simian/human immunodeficiency virus effectively produces infectious virions compared with a less pathogenic virus in cell culture2017

    • Author(s)
      Iwanami, S., Kakizoe, Y., Morita, S., Miura, T., Nakaoka, S., and Iwami, S.
    • Journal Title

      Theoretical Biology and Medical Modelling

      Volume: 印刷中

    • NAID

      120006305768

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Generation of a neutralization-resistant CCR5 tropic SHIV-MK38 molecular clone, a derivative of SHIV-89.6.2016

    • Author(s)
      Ishida Yuki, Yoneda Mai, Otsuki Hiroyuki, Watanabe Yuji, Kato Fumihiro, Matuura Kanako, Kikukawa Minako, Matsushita Shuzo, Hishiki Takayuki, Igarashi Tatsuhiko, Miura Tomoyuki.
    • Journal Title

      J Gen Virol

      Volume: 97(5) Issue: 5 Pages: 1249-60

    • DOI

      10.1099/jgv.0.000421

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A minimally cytotoxic CD4 mimic as an HIV entry inhibitor2016

    • Author(s)
      Takaaki Mizuguchi, Shigeyoshi Harada, Tomoyuki Miura, Nami Ohashi, Tetsuo Narumi, Hiromi Mori, Yu Irahara, Yuko Yamada, Wataru Nomura, Shuzo Matsushita, Kazuhisa Yoshimura, Hirokazu Tamamura
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 26 Issue: 2 Pages: 397-400

    • DOI

      10.1016/j.bmcl.2015.11.103

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 霊長類モデルを用いたHIV感染症の予防・治療法開発2016

    • Author(s)
      三浦智行
    • Journal Title

      公益社団法人日本実験動物学会編: 実験動物感染症と感染症動物モデルの現状

      Volume: - Pages: 99-105

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Association of lymph-node antigens with lower Gag-specific central-memory and higher Env-specific effector-memory CD8+ T-cell frequencies in a macaque AIDS model2016

    • Author(s)
      Ishii H, Matsuoka S, Nomura T, Nakamura M, Shiino T, Sato Y, Iwata-Yoshikawa N, Hasegawa H, Mizuta K, Sakawaki H, Miura T, Koyanagi Y, Naruse TK, Kimura A, Matano T
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 30153-30153

    • DOI

      10.1038/srep30153

    • NAID

      120006346255

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Tier1B SHIV感染ザルにおける抗HIV-1 Tier2中和抗体の誘導2019

    • Author(s)
      姫野愛、石田裕樹、森ひろみ、松浦嘉奈子、菊川美奈子、阪脇廣美、三浦智行
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] SIV感染サル化マウスのAIDS病態モデルとしての有用性の検討2019

    • Author(s)
      横山温香、陣野萌恵、関根将、三浦智行、伊吹謙太郎
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ワクチンによって誘導されたGagエピトープ特異的CD8陽性T細胞の交差性2019

    • Author(s)
      野村拓志、寺原和孝、石井洋、山本浩之、三浦智行、俣野哲朗
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Protective effects of immunization using urease-deficient BCG, vaccinia LC16m8d, and Sendai virus expressing SIV genes2019

    • Author(s)
      Shida, H., Kato, S., Okamura, T., Mukai, T., Inoue, M., Shu, T., Miura, T., Yasutomi, Y., Matsuo, K.
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 霊長類モデルを用いたHIV感染症の予防・治療法開発2017

    • Author(s)
      三浦智行
    • Organizer
      第26回サル疾病ワークショップ
    • Related Report
      2017 Annual Research Report
  • [Presentation] CCR5指向性サル/ヒト免疫不全ウイルス感染アカゲザル血漿における中和能の進化2017

    • Author(s)
      姫野愛、石田裕樹、森ひろみ、松浦嘉奈子、菊川美奈子、三浦智行
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Induction of mutant epitope-specific CD8+ T cells is an indicator of the beginning of viral control failure in SIV controllers2017

    • Author(s)
      Nomura, T., Ishii, H., Seki, S., Yamamoto, H., Terahara, K., Miura, T., and Matano, T.
    • Organizer
      35th Annual Symposium on Nonhuman Primate Models for AIDS
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 免疫不全ウイルス感染病態研究におけるサル化マウスの有用性の検討2017

    • Author(s)
      陣野萌恵、関根将、横山温香、三浦智行、伊吹謙太郎
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] SIV感染サルをモデルとした中和抗体誘導メカニズムの解析2017

    • Author(s)
      桑田岳夫、佐野雅人、松岡佐織、俣野哲朗、関洋平、明里宏文、三浦智行、松下修三
    • Organizer
      第31回日本エイズ学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 中和抵抗性CCR5指向性サル/ヒト免疫不全ウイルス感染アカゲザル血漿における中和能の広域化2016

    • Author(s)
      姫野愛、石田裕樹、米田舞、松浦嘉奈子、菊川美奈子、三浦智行
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] 中和抵抗性かつCCR5指向性の新規HIV-1rmtの構築2016

    • Author(s)
      川上朗彦、姫野愛、菊川美奈子、石田裕樹、野間口雅子、足立昭夫、三浦智行
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] 中和感受性株SIVsmH635FC感染における中和抵抗性株SIVsmE543交差性中和抗体誘導の経時的解析2016

    • Author(s)
      佐野雅人、桑田岳夫、松岡佐織、関塚剛史、明里宏文、三浦智行、俣野哲朗
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] カニクイザルにおけるR5指向性HIV-1長期潜伏感染の解析2016

    • Author(s)
      Seki, Y., Saito, A., Satou, Y., Harada, S., Yoshimura, K., Ode, H., Iwatani, Y., Yoshida, T., Murata, M., Watanabe, Y., Yasutomi, Y., Matano, T., Miura, T., Akari, H.
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] HIV-1ワクチン開発とその課題2016

    • Author(s)
      志田壽利、加藤誠一、保富康宏、松尾和浩、三浦智行、五十嵐樹彦、張険峰、井上誠、成瀬妙子、木村彰方
    • Organizer
      第25回日本組織適合性学会
    • Place of Presentation
      札幌
    • Year and Date
      2016-10-22
    • Related Report
      2016 Annual Research Report
    • Invited

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Published: 2016-04-21   Modified: 2020-03-30  

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