Study about HIV-1 escape mutation exerted on AIDS clinical condition progress

• Project/Area Number: 26293240
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Kumamoto University
• Principal Investigator: Takiguchi Masafumi 熊本大学, エイズ学研究センター, 教授 (00183450)
• Co-Investigator(Renkei-kenkyūsha): OKA Shinichi 国立国際医療研究センター, エイズ治療・研究開発センター, センター長 (20194326)
• Research Collaborator: KUSE Nozomi ; MURAKOSHI Hayato ; CHIKATA Takayuki ; ZABRINA Burumme
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2016: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: AIDS / HIV-１ / T細胞 / 変異 / HIV-1 / ＡＩＤＳ / ＨＩＶ－１ / Ｔ細胞

Outline of Final Research Achievements

We investigated the role of escape mutants selected by HIV-1-specific CTLs in progression to AIDS. First, we analyzed HLA-associated mutations in 430 HIV-1-infected Japanese individuals. We found 283 HLA-associated mutations in our cohort. Five mutations associated with HLA-B52/C12 is associated with lower plasma viral load. In vitro analysis confirmed that these mutations were selected by HLA-B*52:01- or C*12:02-restricted CTLs and that the mutant viruses having these mutation has lower replication capacity than wild-type ones. The present study demonstrated that HLA-B52/C12 may control HIV-1 replication in individuals having these protective alleles and the mutation selected by these CTLs has low replication capacity, This is the mechanism of slow progression to AIDS in individuals having protective haplotype, HLA-B:52:01-C*12:02.

Research Products

• [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
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] HIV-1 control by NK cells via reduced interaction between KIR2DL2 and HLA-C*12:02/C*14:03 (2016)
  • Author(s): Lin Z, Kuroki K, Kuse N, Sun X, Akahoshi T, Qi Y, Chikata T, Naruto T, Koyanagi M, Murakoshi H, Gatanaga H, Oka S, Carrington M, Maenaka K, Takiguchi M.
  • Journal Title: Cell Rep. Volume: 17 (9) Issue: 9 Pages: 2210-2220
  • DOI: 10.1016/j.celrep.2016.10.075
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Effects of a Single Escape Mutation on T Cell and HIV-1 Co-adaptation. (2016)
  • Author(s): Sun X, Shi Y, Akahoshi T, Fujiwara M, Gatanaga H, Schönbach C, Kuse N, Appay V, Gao GF, Oka S, Takiguchi M.
  • Journal Title: Cell Rep. Volume: 15 (10） Issue: 10 Pages: 2279-91
  • DOI: 10.1016/j.celrep.2016.05.017
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Clinical Control of HIV-1 by Cytotoxic T Cells Specific for Multiple Conserved Epitopes. (2015)
  • Author(s): Hayato Murakoshi, Tomohiro Akahoshi, Madoka Koyanagi, Takayuki Chikata, Takuya Naruto, Rie Maruyama, Yoshiko Tamura, Naoki Ishizuka, Hiroyuki Gatanaga, Shinichi Oka, and Masafumi Takiguchi
  • Journal Title: J. Virol. Volume: 89 Issue: 10 Pages: 5330-9
  • DOI: 10.1128/jvi.00020-15
  • Peer Reviewed
• [Journal Article] Lack of a significant impact of Gag-Protease-mediated HIV-1 replication capacity on clinical parameters in treatment-naive Japanese individuals (2015)
  • Author(s): Sakai K, Chikata T, Brumme ZL, Brumme CJ, Gatanaga H, Oka S, Takiguchi M
  • Journal Title: Retrovirology Volume: 12 Issue: 1 Pages: 98-98
  • DOI: 10.1186/s12977-015-0227-8
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Host-Specific Adaptation of HIV-1 Subtype Bin the Japanese Population (2014)
  • Author(s): Takayuki Chikata, Jonathan M. Carlson, Yoshiko Tamura, Mohamed Ali Borghan, Takuya Naruto, Masao Hashimoto, Hayato Murakoshi, Anh Q. Le, Simon Mallal, Mina John, Hiroyuki Gatanaga, Shinichi Oka, Zabrina L. Brumme, Masafumi Takiguchi
  • Journal Title: Journal of Virology Volume: 88巻 Issue: 9 Pages: 4764-4775
  • DOI: 10.1128/jvi.00147-14
  • Peer Reviewed
• [Presentation] Control of HIV-1 by NK cells via KIR-2DL2 and 2 HLA-C alleles (2016)
  • Author(s): Zhansong Lin, Kimiko Kuroki, Nozomi Kuse, Xiaoming Sun, Tomohiro Akahoshi, Ying Qi, Takayuki Chikata, Takuya Naruto, Madoka Koyanagi, Hayato Murakoshi, Hiroyuki Gatanaga, Shinichi Oka, Mary Carrington, Katsumi Maenaka, Masafumi Takiguchi
  • Organizer: 2nd Kumamoto IRCMS International Symposium and 17th Kumamoto AIDS Seminar
  • Place of Presentation: Kumamoto Kenmin Koryu Kaikan-Parea, Kumamoto, Japan
  • Year and Date: 2016-10-31
  • Int'l Joint Research
• [Presentation] Co-evolution between HIV-1 escape mutant and HIV-1-specific T cells (2016)
  • Author(s): Tomohiro Akahoshi, Masao Hashimoto, Takayuki Chikata, Hayato Murakoshi, Nozomi Kuse, Yoshiko Tamura, Hiroyuki Gatanaga, Shinichi Oka, and Masafumi Takiguchi
  • Organizer: 2nd Kumamoto IRCMS International Symposium and 17th Kumamoto AIDS Seminar
  • Place of Presentation: Kumamoto Kenmin Koryu Kaikan-Parea, Kumamoto, Japan
  • Year and Date: 2016-10-31
  • Int'l Joint Research
• [Presentation] Impaired Effect of HLA-A*24:02-Associated Mutation on HLA-B*35:01-Associated HIV-1 Control (2016)
  • 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,, Masafumi Takiguchi
  • Organizer: HIVR4P 2016
  • Place of Presentation: Sheraton Grand Chicago, Chicago, USA
  • Year and Date: 2016-10-17
  • Int'l Joint Research
• [Presentation] Control of HIV-1 accumulating escape mutations by CTLs specific for conserved and cross-reactive epitopes (2016)
  • Author(s): Masafumi Takiguchi
  • Organizer: The U.S. Japan Cooperative Medical Sciences Program presents 50th Anniversary Celebration
  • Place of Presentation: Bethesda North Marriott Hotel and Conference Center (Bethesda, MD, USA)
  • Year and Date: 2016-01-13
  • Int'l Joint Research / Invited
• [Presentation] Control of HIV-1 by cytotoxic T cells specific for multiple conserved epitopes (2015)
  • Author(s): Hayato Murakoshi, Tomohiro Akahoshi, Madoka Koyanagi, Takayuki Chikata, Takuya Naruto, Rie Maruyama, Yoshiko Tamura, Hiroyuki Gatanaga, Shinichi Oka, Masafumi Takiguchi
  • Organizer: The 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention
  • Place of Presentation: Vancouver (Canada)
  • Year and Date: 2015-07-19 – 2015-07-22
• [Presentation] Control of HIV-1 by cytotoxic T cells specific for multiple conserved epitopes (2015)
  • Author(s): Hayato Murakoshi, Tomohiro Akahoshi, Madoka Koyanagi, Takayuki Chikata, Takuya Naruto, Rie Maruyama, Yoshiko Tamura, Hiroyuki Gatanaga, Shinichi Oka, Masafumi Takiguchi
  • Organizer: The 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015)
  • Place of Presentation: Vancouver Convention Centre (Vancouver, BC, Canada)
  • Year and Date: 2015-07-19
  • Int'l Joint Research
• [Presentation] Effective control of HIV-1 by cytotoxic T cells specific for multiple conserved epitopes (2014)
  • Author(s): Hayato Murakoshi, Tomohiro Akahoshi, Madoka Koyanagi, Takayuki Chikata, and Masafumi Takiguchi
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 国立京都国際会館（京都府・京都市）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] The impact of amino-acid substitution at a position outside the peptide binding groove of HLA-C subtypes in HIV-1-specific T cell recognition (2014)
  • Author(s): Takayuki Chikata, Hayato Murakoshi, Madoka Koyanagi, Tomohiro Akahoshi, Shinichi Oka, and Masafumi Takiguchi
  • Organizer: 第15回熊本エイズセミナー
  • Place of Presentation: 阿蘇リゾートグランヴィリオホテル (熊本県・阿蘇市)
  • Year and Date: 2014-10-01 – 2014-10-03
• [Presentation] Effective control of HIV-1 by cytotoxic T cells specific for multiple conserved epitopes (2014)
  • Author(s): Hayato Murakoshi, Tomohiro Akahoshi, Madoka Koyanagi, Takayuki Chikata, Takuya Naruto, Rie Maruyama, Yoshiko Tamura, Hiroyuki Gatanaga, Shinichi Oka, and Masafumi Takiguchi
  • Organizer: 第15回熊本エイズセミナー
  • Place of Presentation: 阿蘇リゾートグランヴィリオホテル (熊本県・阿蘇市)
  • Year and Date: 2014-10-01 – 2014-10-03
• [Presentation] 日本人HIV-1慢性感染者におけるHLAに関連したHIV-1多型の解析と非アジア人コホートとの比較解析 (2014)
  • Author(s): 近田 貴敬, Jonathan M Carlson, 田村 美子, Mohamed Ali Borghan, 成戸 卓也, 端本 昌夫, 村越 勇人, Anh Q. Le, Simon Mallal, Mina John, 潟永 博之, 岡 慎一, Zabrina L Brumme, 滝口 雅文
  • Organizer: 第16回白馬シンポジウム
  • Place of Presentation: 熊本大学山崎記念館（熊本県・熊本市）
  • Year and Date: 2014-06-13 – 2014-06-14
• [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
• [Remarks] 滝口プロジェクト研究室ホームページ
  • URL: http://www.caids.kumamoto-u.ac.jp/data/takiguchi/
• [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