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Study on HIV-1-specific cytotoxic T lymphocytes responsible for AIDS progression in HIV-1-infected individuals

Research Project

Project/Area Number 15K19588
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Infectious disease medicine
Research InstitutionKumamoto University

Principal Investigator

MURAKOSHI HAYATO  熊本大学, エイズ学研究センター, 特任講師 (60646123)

Research Collaborator GATANAGA Hiroyuki  
CHIKATA Takayuki  
AKAHOSHI Tomohiro  
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords細胞傷害性T細胞 / HIV / HLA
Outline of Final Research Achievements

To clarify this mechanism, we identified HLA-B*35:01-restricted epitope-specific CD8+ T cells controlling HIV-1 in 63 HIV-1 clade B-infected Japanese individuals having HLA-B*35:01 and further analyzed the effect of mutations within the epitopes on the T cell responses. The T cell responses to GagNY9, PolVY10, NefRY11, or YF9 epitopes were significantly associated with low plasma viral load. A breadth of the T cell responses to these 4 epitopes was inversely correlated with it. The control of HIV-1 by YF9-specific T cells are impaired by NefY135F mutation associated with HLA-A*24:02. The ex vivo longitudinal analysis of the YF9-specific T cells showed that the Y135F mutant-specific T cells and wild type-specific/cross-reactive T cells were elicited before and after an emergence of the mutant virus. However, the former T cells failed to control HIV-1 replication whereas the latter T cells contributed to the control of HIV-1.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (18 results)

All 2017 2016 2015 Other

All Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Acknowledgement Compliant: 4 results) Presentation (12 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Remarks (2 results)

  • [Journal Article] Accumulation of Pol Mutations Selected by HLA-B*52:01-C*12:02 Protective Haplotype-Restricted Cytotoxic T Lymphocytes Causes Low Plasma Viral Load Due to Low Viral Fitness of Mutant Viruses.2017

    • Author(s)
      Murakoshi H, Koyanagi M, Chikata T, Rahman MA, Kuse N, Sakai K, Gatanaga H, Oka S, Takiguchi M.
    • Journal Title

      J Virol.

      Volume: 91(4) Issue: 4

    • DOI

      10.1128/jvi.02082-16

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Novel conserved-region T-cell mosaic vaccine with high global HIV-1 coverage is recognized by protective responses in untreated infection2016

    • Author(s)
      Beatrice Ondondo, Hayato Murakoshi, Genevieve Clutton, Sultan Abdul-Jawad, Edmund G.-T. Wee, Hiroyuki Gatanaga, Shinichi Oka, Andrew J. McMichael, Masafumi Takiguchi, Bette Korber and Tomas Hanke
    • Journal Title

      Molecular Therapy

      Volume: 24 Issue: 4 Pages: 832-842

    • DOI

      10.1038/mt.2016.3

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] A strong association of HLA-associated Pol and Gag mutations with clinical parameters2016

    • Author(s)
      Giang Van Tran,* Takayuki Chikata,* Jonathan M. Carson, Hayato Murakoshi, Dung Hoai Nguyen, Yoshiko Tamura, Tomohiro Akahoshi, Nozomi Kuse, Keiko Sakai, Sachiko Sakai, Kyle Cobarrubias, Shinichi Oka, Zabrina L. Brumme, Kinh Van Nguyen, and Masafumi Takiguchi, (*Equal contribution)
    • Journal Title

      AIDS

      Volume: 30 Issue: 5 Pages: 681-689

    • DOI

      10.1097/qad.0000000000000969

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Different Effects of Nonnucleoside Reverse Transcriptase Inhibitor Resistance Mutations2015

    • Author(s)
      Nozomi Kuse*, Mohammad Arif Rahman*, Hayato Murakoshi*, Giang Van Tran, Takayuki Chikata, Madoka Koyanagi, Kinh Van Nguyen, Hiroyuki Gatanaga, Shinichi Oka, and Masafumi Takiguchi, (*Equal contribution)
    • Journal Title

      Journal of Virology

      Volume: 89 Issue: 14 Pages: 7363-7372

    • DOI

      10.1128/jvi.00974-15

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Impact of a Single HLA-A*24:02-associated Escape Mutation on HLA-B*35:01-associated HIV-1 Control and T cell Adaptation2016

    • Author(s)
      Hayato Murakoshi, Tomohiro Akahoshi, Madoka Koyanagi, Takayuki Chikata, Katherine L James, Yoshiko Tamura, Nozomi Kuse, Xiaoming Sun, Hiroyuki Gatanaga, Sarah L Rowland-Jones, Shinichi Oka, and Masafumi Takiguchi
    • Organizer
      第30回日本エイズ学会学術集会・総会
    • Place of Presentation
      鹿児島県鹿児島市(かごしま県民交流センター)
    • Year and Date
      2016-11-24
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ベトナム人HIV-1サブタイプA/E感染者コホートにおけるエイズ病態進行に関与するHLAアリルの探索2016

    • Author(s)
      近田 貴敬, Giang Van Tran, 村越 勇人, 田村 美子, 赤星 智寛, 久世 望, 阪井 恵子, 小柳 円, Kinh Van Nguyen, 滝口 雅文
    • Organizer
      第30回日本エイズ学会学術集会・総会
    • Place of Presentation
      鹿児島県鹿児島市(かごしま県民交流センター)
    • Year and Date
      2016-11-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] HIV-1と特異的CTLの相互適応2016

    • Author(s)
      赤星 智寛, 端本 昌夫, 村越 勇人, 近田 貴敬, 田村 美子, 潟永 博之, 岡 慎一, 滝口 雅文
    • Organizer
      第30回日本エイズ学会学術集会・総会
    • Place of Presentation
      鹿児島県鹿児島市(かごしま県民交流センター)
    • Year and Date
      2016-11-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] Impaired Effect of HLA-A*24:02-Associated Mutation on HLA-B*35:01-Associated HIV-1 Control2016

    • Author(s)
      Hayato Murakoshi, Tomohiro Akahoshi, Madoka Koyanagi, Takayuki Chikata, Katherine L James, Nozomi Kuse, Yoshiko Tamura, Sarah L Rowland-Jones, Shinichi Oka, Hiroyuki Gatanaga, and Masafumi Takiguchi
    • Organizer
      HIVR4P 2016
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2016-10-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ベトナム人HIV-1感染者に見られるHIV-1感染制御に関与したHIV-1特異的細胞傷害性T細胞2015

    • Author(s)
      田村 美子, 村越 勇人, 丸山 理恵, Dung Hoai Nguyen, Giang Van Tran, 赤星 智寛, 久世 望, 近田 貴敬, 阪井 恵子, 小柳 円, 酒井 幸子, 岡 慎一, Kinh Van Nguyen, 滝口 雅文
    • Organizer
      第29回日本エイズ学会学術集会・総会
    • Place of Presentation
      東京都文京区(東京ドームホテル)
    • Year and Date
      2015-11-30
    • Related Report
      2015 Research-status Report
  • [Presentation] ベトナム人HIV-1 subtype A/E 感染者コホートにおけるHLA-associated polymorphism の同定2015

    • Author(s)
      近田 貴敬, Giang Van Tran, Jonathan Carlson, 村越 勇人, Dung Hoai Nguyen, 田村 美子, 赤星 智寛, 久世 望, 阪井 恵子, 小柳 円, 酒井 幸子, Kyle Cobarrubias, 岡 慎一, Zabrina Brumme, Kinh Van Nguyen, 滝口 雅文
    • Organizer
      第29回日本エイズ学会学術集会・総会
    • Place of Presentation
      東京都文京区(東京ドームホテル)
    • Year and Date
      2015-11-30
    • Related Report
      2015 Research-status Report
  • [Presentation] ベトナム人慢性HIV-1感染者におけるHIV-1特異的細胞傷害性T細胞の網羅的解析2015

    • Author(s)
      村越 勇人, 田村 美子, 丸山 理恵, Dung Hoai Nguyen, Giang Van Tran, 赤星 智寛, 久世 望, 阪井 恵子, 小柳 円, 酒井 幸子, 岡 慎一, Kinh Van Nguyen, 滝口 雅文
    • Organizer
      第29回日本エイズ学会学術集会・総会
    • Place of Presentation
      東京都文京区(東京ドームホテル)
    • Year and Date
      2015-11-30
    • Related Report
      2015 Research-status Report
  • [Presentation] The impact of one amino-acid substitution outside the binding groove between HLA-C*03 subtypes in binding of HIV-1 peptide to the HLA molecules2015

    • Author(s)
      Takayuki Chikata, Hayato Murakoshi, Madoka Koyanagi, Tomohiro Akahoshi, and Masafumi Takiguchi
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      北海道札幌市 (札幌コンベンションセンター)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report
  • [Presentation] An escape mutation selected by HIV-1-specific CTLs generates a novel CTL epitope2015

    • Author(s)
      Tomohiro Akahoshi, Madoka Koyanagi, Hayato Murakoshi, Nozomi Kuse, and Masafumi Takiguchi
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      北海道札幌市 (札幌コンベンションセンター)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report
  • [Presentation] HIV-1-specific CD8+ T cells responsible for rapid AIDS progression in HIV-1-infected Japanese individuals carrying HLA-B*35:012015

    • Author(s)
      Hayato Murakoshi, Madoka Koyanagi, Tomohiro Akahoshi, Takayuki Chikata, and Masafumi Takiguchi
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      北海道札幌市 (札幌コンベンションセンター)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report
  • [Presentation] 7.Identification of HLA-associated polymorphisms in a cohort of HIV-1 subtype A/E infection2015

    • Author(s)
      Tran Van Giang, Takayuki Chikata, Yoshiko Tamura, Tomohiro Akahoshi, Hayato Murakoshi, Nozomi Kuse, Shinichi Oka, Keiko Sakai, Nguyen Van Kinh, Masafumi Takiguchi
    • Organizer
      IAS 2015
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2015-07-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 1.Control of HIV-1 by cytotoxic T cells specific for multiple conserved epitopes2015

    • Author(s)
      Hayato Murakoshi, Tomohiro Akahoshi, Madoka Koyanagi, Takayuki Chikata, Takuya Naruto, Rie Maruyama, Yoshiko Tamura, Hiroyuki Gatanaga, Shinichi Oka, and Masafumi Takiguchi
    • Organizer
      IAS 2015
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2015-07-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Remarks] 熊本大学エイズ学研究センター滝口プロジェクト研究室

    • URL

      http://www.caids.kumamoto-u.ac.jp/data/takiguchi/default.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 熊本大学エイズ学研究センター 滝口プロジェクト研究室

    • URL

      http://www.caids.kumamoto-u.ac.jp/data/takiguchi/default.html

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2018-03-22  

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