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Strategies overcome Multi-drug resistance in HIV: GAPDH as a restriction factor to suppress the packaging of the primer tRNA for reverse transcription

Research Project

Project/Area Number 16K18922
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Environmental and hygienic pharmacy
Research InstitutionKumamoto University

Principal Investigator

KISHIMOTO Naoki  熊本大学, 大学院生命科学研究部(薬), 助教 (80756148)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsHIV / 宿主因子 / 逆転写反応 / tRNA / 逆転写 / HIV-1 / GAPDH / tRNALys3 / ウイルス / 感染症 / 根治療法 / 逆転写過程
Outline of Final Research Achievements

GAPDH, a host protein, suppresses the packaging of tRNALys3, which is required for effective viral reverse transcription as a primer. Here, I investigated the mechanism of tRNALys3-packaging suppression by GAPDH. As results, GAPDH interacts with both matrix region and capsid region of viral precursor protein. Interestingly, GAPDH oligomerization prevents tRNALys3 packaging into virions. These findings indicate that utilization of the role of GAPDH in tRNALys3 packaging is effective for preventing initiation of HIV reverse transcription.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (21 results)

All 2018 2017 2016 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (16 results) (of which Int'l Joint Research: 2 results) Remarks (1 results)

  • [Journal Article] Virion-Packaged Pyruvate Kinase Muscle Type 2 Affects Reverse Transcription Efficiency of Human Immunodeficiency Virus Type 1 by Blocking Virion Recruitment of tRNA<sup>Lys3</sup>2018

    • Author(s)
      Mouree KR, Kishimoto N, Iga N, Kirihara C, Yamamoto K, Takamune N, Misumi S.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 41 Issue: 4 Pages: 612-618

    • DOI

      10.1248/bpb.b17-00991

    • NAID

      130006602500

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Trametinib suppresses HIV-1 replication by interfering with the disassembly of human immunodeficiency virus type 1 capsid core2018

    • Author(s)
      Dochi T, Akita A, Kishimoto N, Takamune N, Misumi S.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 495 Issue: 2 Pages: 1846-1850

    • DOI

      10.1016/j.bbrc.2017.11.177

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Virion-incorporated alpha-enolase suppresses the early stage of HIV-1 reverse transcription.2017

    • Author(s)
      Kishimoto N, Iga N, Yamamoto K, Takamune N, Misumi S.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 484 Pages: 278-284

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The C-terminal domain of glyceraldehyde 3-phosphate dehydrogenase plays an important role in suppression of tRNALys3 packaging into human immunodeficiency virus type-1 particles.2016

    • Author(s)
      Kishimoto N, Onitsuka-Kishimoto A, Iga N, Takamune N, Shoji S, Misumi S.
    • Journal Title

      Biochem. Biophy. Rep.

      Volume: 8 Pages: 325-332

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] HIV-1標的細胞内における解糖系酵素ENO1の抗ウイルス作用2017

    • Author(s)
      山本 謙吾、岸本 直樹、伊賀 望、高宗 暢暁、三隅 将吾
    • Organizer
      平成29年度 日本生化学会九州支部例会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Alpha-enolase はHIV-1複製に対抗する二つの制御機能を兼ね備える2017

    • Author(s)
      山本 謙吾、岸本 直樹、高宗 暢暁、三隅 将吾
    • Organizer
      第41回 蛋白質と酵素の構造と機能に関する九州シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] HIVプロテオミクスによるHIV-1カプシドタンパク質の解析2017

    • Author(s)
      下賀 悠平、岸本 直樹、高宗 暢暁、三隅 将吾
    • Organizer
      第41回 蛋白質と酵素の構造と機能に関する九州シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] Alpha-enolase showed negative effects on HIV-1 replication2017

    • Author(s)
      Naoki Kishimoto, Kengo Yamamoto, Nozomi Iga, Nobutoki Takamune, Shogo Misumi
    • Organizer
      The 65th ANNUAL MEETING OF THE JAPANESE SOCIETY FOR VIROLOGY
    • Related Report
      2017 Annual Research Report
  • [Presentation] PKM2 expressed in HIV-1 producer cell affects the infectivity of progeny viruses by targeting reverse transcription step2017

    • Author(s)
      Kumkum Rahman Mouree, Naoki Kishimoto, Nobutoki Takamune Shogo Misumi
    • Organizer
      18th KUMAMOTO AIDS Seminar
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] GAPDHおよびENO1はmoonlightingタンパク質としてHIV複製を制御する2017

    • Author(s)
      岸本 直樹、伊賀 望、山本 謙吾、高宗 暢暁、三隅 将吾
    • Organizer
      2017年度 生命科学系学会合同年次大会(第40回日本分子生物学会年会、第90回日本生化学会大会)
    • Related Report
      2017 Annual Research Report
  • [Presentation] HIVカプシドタンパク質Thr216リン酸化は脱殻反応のタイミングを調節する2016

    • Author(s)
      曽根将平、堂地赳生、高宗暢暁、岸本直樹、三隅将吾
    • Organizer
      第33回 日本薬学会九州支部大会
    • Place of Presentation
      鹿児島(鹿児島大学郡元キャンパス)
    • Year and Date
      2016-12-03
    • Related Report
      2016 Research-status Report
  • [Presentation] HIV-1カプシドタンパク質と相互作用を有する新規宿主因子の探索2016

    • Author(s)
      山田芽衣、岸本直樹、高宗暢暁、三隅将吾
    • Organizer
      第30回 日本エイズ学会学術集会
    • Place of Presentation
      鹿児島(かごしま県民交流センター)
    • Year and Date
      2016-11-24
    • Related Report
      2016 Research-status Report
  • [Presentation] HIV-1 p2gag peptide plays a role in the ATP production in the post-entry step2016

    • Author(s)
      Naoki Kishimoto, Nobutoki Takamune, Shinya Suzu, Shogo Misumi
    • Organizer
      2nd Kumamoto IRCMS International Symposium and 17th KUMAMOTO AIDS Seminar
    • Place of Presentation
      Kumamoto (Kumamoto Kenmin Koryukan-Parea)
    • Year and Date
      2016-10-31
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Phosphorylation of human immunodeficiency virus type-1 capsid protein at threonine 216 is required for the uncoating2016

    • Author(s)
      Shohei Sone, Naoki Kishimoto, Dochi Takeo, Nobutoki Takamune, Shogo Misumi
    • Organizer
      2nd Kumamoto IRCMS International Symposium and 17th KUMAMOTO AIDS Seminar
    • Place of Presentation
      Kumamoto (Kumamoto Kenmin Koryukan-Parea)
    • Year and Date
      2016-10-31
    • Related Report
      2016 Research-status Report
  • [Presentation] HIV-1 capsidタンパク質の機能を制御する新規宿主因子の探索2016

    • Author(s)
      秋田彩乃、堂地赳生、岸本直樹、高宗暢暁、三隅将吾
    • Organizer
      第89回日本生化学会
    • Place of Presentation
      宮城(仙台国際センター/東北大学川内北キャンパス)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 解糖系酵素GAPDH、ENO1がHIV-1粒子内に取込まれる意義の解明2016

    • Author(s)
      伊賀望、岸本直樹、鬼塚彩乃、桐原知江、高宗暢暁、庄司省三、三隅将吾
    • Organizer
      第15回 次世代を担う若手ファーマ・バイオフォーラム2016
    • Place of Presentation
      大阪(大阪大学大学院薬学研究科)
    • Year and Date
      2016-09-10
    • Related Report
      2016 Research-status Report
  • [Presentation] HIV脱殻過程に要求されるカプシドタンパク質Thr216リン酸化2016

    • Author(s)
      曽根将平、堂地赳生、高宗暢暁、岸本直樹、三隅将吾
    • Organizer
      第15回 次世代を担う若手ファーマ・バイオフォーラム2016
    • Place of Presentation
      大阪(大阪大学大学院薬学研究科)
    • Year and Date
      2016-09-10
    • Related Report
      2016 Research-status Report
  • [Presentation] HIV p2 peptideによる電子伝達系複合体IV活性調節とウイルス複製2016

    • Author(s)
      岸本直樹、小川実菜子、竹元雄輝、角真太郎、井上大奨、高宗暢暁、庄司省三、鈴伸也、三隅将吾
    • Organizer
      平成28年度 日本生化学会九州支部例会
    • Place of Presentation
      鹿児島(鹿児島大学郡元キャンパス)
    • Year and Date
      2016-05-14
    • Related Report
      2016 Research-status Report
  • [Presentation] HIV-1病原性因子Nefの翻訳に重要な領域と感染性への影響2016

    • Author(s)
      渡邉俊輝、長峰啓志郎、岸本直樹、三隅将吾、高宗暢暁
    • Organizer
      平成28年度 日本生化学会九州支部例会
    • Place of Presentation
      鹿児島(鹿児島大学郡元キャンパス)
    • Year and Date
      2016-05-14
    • Related Report
      2016 Research-status Report
  • [Presentation] HIV-1 capsid タンパク質と相互作用するHIV-1感染制御因子の探索2016

    • Author(s)
      秋田彩乃、堂地赳生、岸本直樹、高宗暢暁、三隅将吾
    • Organizer
      平成28年度 日本生化学会九州支部例会
    • Place of Presentation
      鹿児島(鹿児島大学郡元キャンパス))
    • Year and Date
      2016-05-14
    • Related Report
      2016 Research-status Report
  • [Remarks] 熊本大学大学院生命科学研究部環境分子保健学分野ウェブページ

    • URL

      http://www.pharm.kumamoto-u.ac.jp/Labs/emhs/

    • Related Report
      2017 Annual Research Report 2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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