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Study of virus reservoir injury treatment on primate AIDS model

Research Project

Project/Area Number 19H03146
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 42040:Laboratory animal science-related
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)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2020: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Keywords多剤併用療法 / 機能的治癒 / 動物モデル / 感染症 / アカゲザル / HIV / SHIV / エイズ
Outline of Research at the Start

HIV 感染症の機能的治癒達成には、ウイルスを保持する組織および細胞(ウイルスリザーバー)を排除する必要がある。多剤併用療法下でウイルスリザーバーを傷害することで、治療中断後のウイルス制御の可能性をサルエイズモデルにより検証する事を本研究課題の目的とする。具体的には多剤併用療法下のSIV感染サルに対してウイルスリザーバーを傷害する抗体や薬剤を処置した後、多剤併用療法中断後の血中ウイルス量を調べることによってウイルス制御効果の有無を明らかにする。

Outline of Final Research Achievements

We examined the impact of the reduction of systemic CD4-positive T cells, which is considered to be important as a reservoir of HIV, in rhesus monkeys by anti-CD4 antibody administration against virus rebound from reservoir after combind anti-retrovirus therapy interruption. In the result, it was clarified that the effect of systemic CD4-positive T cell reduction for suppressing the viral rebound was little, but viral suppression effect after the rebound was observed in one of three monkeys examined. This is an interesting finding in considering a new treatment of HIV infection.

Academic Significance and Societal Importance of the Research Achievements

エイズ治療研究において機能的治癒に向けた研究は現在最も先端的な研究分野である。本研究計画はサルエイズモデルを用いた実験感染であるため、リザーバー傷害によるコンセプトを実証的に検証する事が出来る。本研究計画を推進した結果、cART 下でプロウイルス保有細胞を傷害する事がHIV 感染症の機能的治癒につながるか、または実際上の効果が無いかが分かる。このとは機能的治癒に向けた戦略策定の上で研究リソースをより正しい方向に集中する助けとなるため、結果がコンセプトの肯定はもちろんであるが否定であってもHIV 感染症制御に貢献出来る。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (19 results)

All 2021 2020 2019

All Journal Article (13 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 13 results,  Open Access: 10 results) Presentation (6 results)

  • [Journal Article] Hybrids of Small-Molecule CD4 Mimics with Polyethylene Glycol Units as HIV Entry Inhibitors2021

    • Author(s)
      Kobayakawa Takuya、Tsuji Kohei、Konno Kiju、Himeno Ai、Masuda Ami、Yang Tingting、Takahashi Kohei、Ishida Yusuke、Ohashi Nami、Kuwata Takeo、Matsumoto Kaho、Yoshimura Kazuhisa、Sakawaki Hiromi、Miura Tomoyuki、Harada Shigeyoshi、Matsushita Shuzo、Tamamura Hirokazu
    • Journal Title

      Journal of Medicinal Chemistry

      Volume: 64 Issue: 3 Pages: 1481-1496

    • DOI

      10.1021/acs.jmedchem.0c01153

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Potent Anti-Simian Immunodeficiency Virus Neutralizing Antibody Induction Associated with a Germ Line Immunoglobulin Gene Polymorphism in Rhesus Macaques2021

    • Author(s)
      Matsuoka Saori、Kuwata Takeo、Ishii Hiroshi、Sekizuka Tsuyoshi、Kuroda Makoto、Sano Masato、Okazaki Midori、Yamamoto Hiroyuki、Shimizu Mikiko、Matsushita Shuzo、Seki Yohei、Saito Akatsuki、Sakawaki Hiromi、Hirsch Vanessa M.、Miura Tomoyuki、Akari Hirofumi、Matano Tetsuro
    • Journal Title

      Journal of Virology

      Volume: 95 Issue: 7

    • DOI

      10.1128/jvi.02455-20

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CD8 T Cells Show Protection against Highly Pathogenic Simian Immunodeficiency Virus (SIV) after Vaccination with SIV Gene-Expressing BCG Prime and Vaccinia Virus/Sendai Virus Vector Boosts2021

    • Author(s)
      Seiichi Kato, Hisatoshi Shida, Tomotaka Okamura, Xianfeng Zhang, Tomoyuki Miura, Tetsu Mukai, Makoto Inoue, Tsugumine Shu, Taeko K Naruse, Akinori Kimura, Yasuhiro Yasutomi, Kazuhiro Matsuo
    • Journal Title

      Journal of Virology

      Volume: 95 Issue: 4

    • DOI

      10.1128/jvi.01718-20

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of macrophages with altered viral sensitivity from genome-edited rhesus macaque iPSCs to model human disease2021

    • Author(s)
      Iwamoto Yoshihiro、Seki Yohei、Taya Kahoru、Tanaka Masahiro、Iriguchi Shoichi、Miyake Yasuyuki、Nakayama Emi E.、Miura Tomoyuki、Shioda Tatsuo、Akari Hirofumi、Takaori-Kondo Akifumi、Kaneko Shin
    • Journal Title

      Molecular Therapy - Methods & Clinical Development

      Volume: 21 Pages: 262-273

    • DOI

      10.1016/j.omtm.2021.03.008

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Neutralization Assay Based on Pseudo-Typed Lentivirus with SARS CoV-2 Spike Protein in ACE2-Expressing CRFK Cells2021

    • Author(s)
      Pisil Yalcin、Shida Hisatoshi、Miura Tomoyuki
    • Journal Title

      Pathogens

      Volume: 10 Issue: 2 Pages: 153-153

    • DOI

      10.3390/pathogens10020153

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Specific Substitutions in Region V2 of gp120 env confer SHIV Neutralisation Resistance2020

    • Author(s)
      Pisil Yalcin、Yazici Zafer、Shida Hisatoshi、Matsushita Shuzo、Miura Tomoyuki
    • Journal Title

      Pathogens

      Volume: 9 Issue: 3 Pages: 181-181

    • DOI

      10.3390/pathogens9030181

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Detection and genotyping of bovine leukemia virus (BLV) in Vietnamese cattle2020

    • Author(s)
      LE Dung Thi、YAMASHITA-KAWANISHI Nanako、OKAMOTO Mari、NGUYEN Son Vu、NGUYEN Nam Huu、SUGIURA Katsuaki、MIURA Tomoyuki、HAGA Takeshi
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 82 Issue: 7 Pages: 1042-1050

    • DOI

      10.1292/jvms.20-0094

    • NAID

      130007882287

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Therapeutic vaccine-mediated Gag-specific CD8+ T-cell induction under anti-retroviral therapy augments anti-virus efficacy of CD8+ cells in simian immunodeficiency virus-infected macaques2020

    • Author(s)
      Nakamura-Hoshi Midori、Takahara Yusuke、Matsuoka Saori、Ishii Hiroshi、Seki Sayuri、Nomura Takushi、Yamamoto Hiroyuki、Sakawaki Hiromi、Miura Tomoyuki、Tokusumi Tsuyoshi、Shu Tsugumine、Matano Tetsuro
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 11394-11394

    • DOI

      10.1038/s41598-020-68267-w

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PIM kinases facilitate lentiviral evasion from SAMHD1 restriction via Vpx phosphorylation2019

    • Author(s)
      Miyakawa Kei、Matsunaga Satoko、Yokoyama Masaru、Nomaguchi Masako、Kimura Yayoi、Nishi Mayuko、Kimura Hirokazu、Sato Hironori、Hirano Hisashi、Tamura Tomohiko、Akari Hirofumi、Miura Tomoyuki、Adachi Akio、Sawasaki Tatsuya、Yamamoto Naoki、Ryo Akihide
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 1844-1844

    • DOI

      10.1038/s41467-019-09867-7

    • NAID

      120006949469

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Revealing uninfected and infected target cell dynamics from peripheral blood data in highly and less pathogenic simian/human immunodeficiency virus infected Rhesus macaque2019

    • Author(s)
      A. Hara, S. Iwanami, Y. Ito, T. Miura, S. Nakaoka and S. Iwami
    • Journal Title

      Journal of Theoretical Biology

      Volume: 479 Pages: 29-36

    • DOI

      10.1016/j.jtbi.2019.07.005

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of inhibitors of dengue viral replication using replicon cells expressing secretory luciferase2019

    • Author(s)
      Kato Fumihiro、Nio Yasunori、Yagasaki Kazumi、Suzuki Rieko、Hijikata Makoto、Miura Tomoyuki、Miyazaki Isao、Tajima Shigeru、Lim Chang-Kweng、Saijo Masayuki、Takasaki Tomohiko、Hishiki Takayuki
    • Journal Title

      Antiviral Research

      Volume: 172 Pages: 104643-104643

    • DOI

      10.1016/j.antiviral.2019.104643

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Protective effects of immunization using urease-deficient BCG, vaccinia LC16m8d, and sendai virus expressing SIV genes.2021

    • Author(s)
      Hisatoshi Shida、Seiichi Kato、Tomotaka Okamura、Tetsu Mukai、Makoto Inoue、Tsugumine Shu、Tomoyuki Miura、Yasuhiro Yasutomi、Kazuhiro Matsuo
    • Organizer
      第34回近畿エイズ研究会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 根治療法の評価研究に有用なHIV潜伏感染霊長類モデルの樹立2021

    • Author(s)
      関 洋平、齊藤 暁、鷲崎 彩夏、原田 恵嘉、村田 めぐみ、引地 優太、吉村 和久、石井 洋、佐藤 賢文、Islam M Saiful、大出 裕高、岩谷 靖雅、芳田 剛、保富 康広、俣野 哲朗、三浦 智行、明里 宏文
    • Organizer
      第34回近畿エイズ研究会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 非ヒト霊長類疾病モデル作成を目的としたゲノム編集アカゲザルiPSCからのウイルス感受性を変化させたマクロファージの再生2021

    • Author(s)
      岩本 芳浩、関 洋平、鷲崎 彩夏、田谷 かほる、田中 正宏、入口 翔一、三宅 康行、中山 英美、三浦 智行、塩田 達夫、明里 宏文、高折 晃史、金子 新
    • Organizer
      第34回近畿エイズ研究会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] SIV感染サル化マウスにおけるIL-6動態の解析2021

    • Author(s)
      西本 佳那子、三浦 弓月、阪脇 廣美、三浦 智行、伊吹 謙太郎
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] エリートコントローラーにおけるloss of controlリスク評価の指標としてのActive reservoir sizeの意義2021

    • Author(s)
      鷲崎 彩夏、関 洋平、齊藤 暁、村田 めぐみ、Weikeat Tan、Anastasiia Kovba、原田 恵嘉、Satyajit Biswas、引地 優太、吉村 和久、佐藤 賢文、Islam M Saiful、大出 裕高、岩谷 靖雅、保富 康広、俣野 哲朗、三浦 智行、明里 宏文
    • Organizer
      第35回日本エイズ学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ARTはエリートコントローラー霊長類モデルにおけるactive reservoir sizeの顕著な低減を引き起こす2021

    • Author(s)
      Anastasiia Kovba、鷲崎 彩夏、関 洋平、Weikeat Tan、村田 めぐみ、松岡 和弘、平野 淳、Satyajit Biswas、齊藤 暁、原田 恵嘉、引地 優太、吉村 和久、石井 洋、大出 裕高、保富 康広、俣野 哲朗、三浦 智行、岩谷 靖雅、明里 宏文
    • Organizer
      第35回日本エイズ学会学術集会
    • Related Report
      2021 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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