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Elucidation of molecular mechanism of HIV cell-to-cell transmission

Research Project

Project/Area Number 16H05198
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionYokohama City University

Principal Investigator

Ryo Akihide  横浜市立大学, 医学研究科, 教授 (20363814)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
KeywordsHIV / 宿主因子 / 細胞-細胞間感染 / プロテオミクス / 分子イメージング / ウイルス / 感染症 / 蛋白質 / プロテオーム / 微生物 / 細胞-細胞間感染 / 微生物学
Outline of Final Research Achievements

It is widely believed that cell-to-cell viral transfer is a major mode of HIV-1 infection in lymphoid tissues and much more efficient for spreading viral particles than cell-free infection. In our present study, we created a HIV-1 molecular clone carrying 24 repeats of the MS2-binding sites in order to monitor the intracellular dynamics of Gag and vRNA in cells. Using this system, we show that the tumor suppressor adenomatous polyposis coli protein (APC) directs the localization and assembly of HIV-1 Gag polyprotein at distinct membrane components to enable the efficient production and spread of infectious viral particles. Furthermore, we newly identified anti-viral host factors that selectively suppress the cell-to-cell transmission of HIV-1.

Academic Significance and Societal Importance of the Research Achievements

細胞間接触により感染細胞から非感染細胞に直接エイズウイルスを受け渡すcell-to-cell感染は通常の感染系の数十倍~数千倍という高効率なウイルス伝播が可能であり、新たな創薬ターゲットであると考えられる。本研究で見いだしたAPCはウイルス構成因子を細胞の特定の場所に集積させることで、HIVのcell-to-cell伝播を制御する宿主因子である。APCの本来の機能を阻害させないで、APCとGagの相互作用を阻止できれば、HIVの効率的な細胞-細胞間伝播が阻止できる可能性がある。ウイルス-宿主間相互作用を抑制する新しいタイプの治療薬開発へ展開が期待される。

Report

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

    (21 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (8 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 8 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (8 results) (of which Invited: 1 results) Remarks (3 results)

  • [Int'l Joint Research] University of Michigan Medical School(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] National University of Singapore(シンガポール)

    • Related Report
      2016 Annual Research Report
  • [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
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Production and characterization of monoclonal antibodies specific for major capsid VP1 protein of trichodysplasia spinulosa-associated polyomavirus.2018

    • Author(s)
      Khatun H, Yamaoka Y, Matsushima Y, Matsunaga S, Kimura H, Ho J, Shuda M, Ryo A.
    • Journal Title

      Microbiol Immunol.

      Volume: 62(12) Issue: 12 Pages: 763-773

    • DOI

      10.1111/1348-0421.12662

    • NAID

      40021778110

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Editorial: Perspectives for the Next Generation of Virus Research: Spearheading the Use of Innovative Technologies and Methodologies2017

    • Author(s)
      Yamamoto Takatoki、Honda Ayae、Sato Toshinori、Ryo Akihide
    • Journal Title

      Frontiers in Microbiology

      Volume: 8 Pages: 758-758

    • DOI

      10.3389/fmicb.2017.00758

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differences in Three-Dimensional Geometric Recognition by Non-Cancerous and Cancerous Epithelial Cells on Microgroove-Based Topography2017

    • Author(s)
      Kushiro Keiichiro、Yaginuma Tomohiro、Ryo Akihide、Takai Madoka
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 4244-4244

    • DOI

      10.1038/s41598-017-03779-6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mutations in genes encoding polycomb repressive complex 2 subunits cause Weaver syndrome2017

    • Author(s)
      Eri Imagawa, Ken Higashimoto, Yasunari Sakai, Chikahiko Numakura, Nobuhiko Okamoto, Satoko Matsunaga, Akihide Ryo, Yoshinori Sato, Masafumi Sanefuji, Kenji Ihara, Yui Takada, Gen Nishimura, Hirotomo Saitsu, Takeshi Mizuguchi, Satoko Miyatake, Mitsuko Nakashima, Noriko Miyake, Hidenobu Soejima, Naomichi Matsumoto
    • Journal Title

      Human Mutation

      Volume: 印刷中 Issue: 6 Pages: 637-648

    • DOI

      10.1002/humu.23200

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Salinomycin kills cancer stem cells by sequestering iron in lysosomes2017

    • Author(s)
      Mai Trang Thi、Hamai Ahmed、Hienzsch Antje、Caneque Tatiana、Muller Sebastian、Wicinski Julien、Cabaud Olivier、Leroy Christine、David Amandine、Acevedo Veronica、Ryo Akihide、Ginestier Christophe、Birnbaum Daniel、Charafe-Jauffret Emmanuelle、Codogno Patrice、Mehrpour Maryam、Rodriguez Raphael
    • Journal Title

      Nature Chemistry

      Volume: 9 Issue: 10 Pages: 1025-1033

    • DOI

      10.1038/nchem.2778

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The tumour suppressor APC promotes HIV-1 assembly via interaction with Gag precursor protein.2017

    • Author(s)
      Miyakawa K, Nishi M, Matsunaga S, Okayama A, Anraku M, Kudoh A, Hirano H, Kimura H, Morikawa Y, Yamamoto N, Ono A, Ryo A.
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 14259-14259

    • DOI

      10.1038/ncomms14259

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] H11/HSPB8 Restricts HIV-2 Vpx to Restore the Anti-Viral Activity of SAMHD1.2016

    • Author(s)
      Kudoh A, Miyakawa K, Matsunaga S, Matsushima Y, Kosugi I, Kimura H, Hayakawa S, Sawasaki T, Ryo A.
    • Journal Title

      Frontiers in Microbiology

      Volume: 7 Pages: 883-883

    • DOI

      10.3389/fmicb.2016.00883

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Role for the Gag-CA linker domain in the late HIV-1 replication phase.2018

    • Author(s)
      駒 貴明, 小谷 治, 土肥直哉, 宮川 敬, 梁 明秀, 横山 勝, 佐藤裕徳, 足立昭夫, 野間口雅子.
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 疾患特異的マーカーとしての抗HTLV-1抗体の血清学的エピトープの検討.2018

    • Author(s)
      松永智子, 菱澤方勝, 高折晃史, 梁明秀.
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Protein Active Arrayを用いたヒト血清中に含まれる抗ウイルス抗体の網羅的検出2017

    • Author(s)
      松永智子, 松島勇紀, 森下了, 木村博一, 梁明秀
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] HIV-1複製後期過程におけるGag-CAリンカー領域内アミノ酸残基S149及びI150の役割2017

    • Author(s)
      駒 貴明, 土肥直哉, 宮川 敬, 梁 明秀, 足立昭夫, 野間口雅子
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 宿主因子APCによるHIV細胞-細胞間伝播制御機構の解明2017

    • Author(s)
      宮川 敬, 梁 明秀
    • Organizer
      第31回日本エイズ学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Overcoming viral evasion from host restriction factors: Targeting HIV accessory proteins.2016

    • Author(s)
      梁 明秀
    • Organizer
      第30回日本エイズ学会学術集会
    • Place of Presentation
      かごしま県民交流センター(鹿児島)
    • Year and Date
      2016-11-24
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] NanoBRET法を用いた生細胞内HIV-1 Gagの多量体化解析および結合宿主因子探索.2016

    • Author(s)
      宮川 敬, 松山慎一郎, 村上 努, 梁 明秀
    • Organizer
      第30回日本エイズ学会学術集会
    • Place of Presentation
      かごしま県民交流センター(鹿児島)
    • Year and Date
      2016-11-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] ケミカルバイオロジーを用いたHIV再活性化のメカニズム解析.2016

    • Author(s)
      岩瀬早織, 宮川 敬, 工藤あゆみ, 梁 明秀
    • Organizer
      第30回日本エイズ学会学術集会
    • Place of Presentation
      かごしま県民交流センター(鹿児島)
    • Year and Date
      2016-11-24
    • Related Report
      2016 Annual Research Report
  • [Remarks] 横浜市立大学大学院医学研究科 微生物学・分子生体防御学

    • URL

      https://www-user.yokohama-cu.ac.jp/~saikin/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 国立研究開発法人日本医療研究開発機構 プレスリリース

    • URL

      https://www.amed.go.jp/news/release_20190423.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 横浜市立大学大学院医学研究科微生物学・分子生体防御学

    • URL

      http://www-user.yokohama-cu.ac.jp/~saikin/

    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2022-01-28  

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