Study on HIV-1-specific cytotoxic T cells effectively controlling HIV-1

• Project/Area Number: 25870550
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Infectious disease medicine; Virology
• Research Institution: Kumamoto University
• Principal Investigator: MURAKOSHI HAYATO 熊本大学, エイズ学研究センター, 産学官連携研究員 (60646123)
• Research Collaborator: GATANAGA Hiroyuki ; CHIKATA Takayuki ; TAMURA Yoshiko
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 細胞傷害性T細胞 / HIV / HLA

Outline of Final Research Achievements

We here sought to identify CD8+ T cells controlling HIV-1 variants in 401 Japanese individuals chronically infected with HIV-1 subtype B, in which protective alleles HLA-B*57 and HLA-B*27 are very rare, by using comprehensive and exhaustive methods. We identified 13 HIV-1 epitope-specific CD8+ T cells controlling HIV-1 in Japanese individuals though 9 of these epitopes were not previously reported. Nine of these epitopes were conserved among HIV-1 subtype B-infected individuals, whereas three out of 4 non-conserved epitopes were cross-recognized by the specific T cells. These findings indicate that these 12 epitopes are strong candidates of antigens for AIDS vaccine. The present study highlighted a strategy to identify CD8+ T cells controlling HIV-1 and demonstrated effective control of HIV-1 by those specific for 12 conserved or cross-reactive epitopes.

Research Products

• [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: Journal of Virology Volume: 印刷中
  • Peer Reviewed
• [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
• [Journal Article] Raltegravir and elvitegravir-resistance mutation E92Q affects HLA-B*40:02-restricted HIV-1-specific CTL recognition (2014)
  • Author(s): Mohammad Arif Rahman, Nozomi Kuse, Hayato Murakoshi, Takayuki Chikata, Hiroyuki Gatanaga, Shinichi Oka, Masafumi Takiguchi
  • Journal Title: Microbes and Infection Volume: 印刷中 Issue: 5 Pages: 434-438
  • DOI: 10.1016/j.micinf.2014.03.003
  • Peer Reviewed
• [Journal Article] Naturally selected rilpivirine-resistant HIV-1 variants by host cellular immunity (2013)
  • Author(s): Hiroyuki Gatanaga, Hayato Murakoshi, Atsuko Hachiya, Tsunefusa Hayashida, Takayuki Chikata, Hirotaka Ode, Kiyoto Tsuchiya, Wataru Sugiura, Masafumi Takiguchi, and Shinichi Oka
  • Journal Title: Clinical Infectious Disease Volume: 57 Issue: 7 Pages: 1051-1055
  • DOI: 10.1093/cid/cit430
  • Peer Reviewed
• [Journal Article] Identification of cross-clade CTL epitopes in HIV-1 clade A/E-infected individuals by using the clade B overlapping peptides (2013)
  • Author(s): Koji Watanabe*, Hayato Murakoshi*, Yoshiko Tamura, Madoka Koyanagi, Takayuki Chikata, Hiroyuki Gatanaga, Shinichi Oka, and Masafumi Takiguchi (*Equal contribution)
  • Journal Title: Microbes and Infection Volume: 15 Issue: 13 Pages: 874-886
  • DOI: 10.1016/j.micinf.2013.08.002
  • Peer Reviewed
• [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] Synergistic effect of multiple CTLs on control of HIV-1 in Japanese individuals carrying HLA-B*35:01 allele associated with rapid disease progression (2013)
  • Author(s): Madoka Koyanagi, Hayato Murakoshi, Hiroyuki Gatanaga, Shinichi Oka and Masafumi Takiguchi
  • Organizer: AIDS Vaccine 2013
  • Place of Presentation: Barcelona, Spain
• [Presentation] Cross-clade CD8+ T cell responses in chronically HIV-1 clade A/E-infected individuals (2013)
  • Author(s): Hayato Murakoshi, Koji Watanabe, Yoshiko Tamura, Madoka Koyanagi, Takayuki Chikata, Hiroyuki Gatanaga, Shinichi Oka and Masafumi Takiguchi
  • Organizer: AIDS Vaccine 2013
  • Place of Presentation: Barcelona, Spain
• [Presentation] HIV-1 polymorphisms associated with 4-digit HLA alleles in Japanese individuals chronically infected with the clade B virus (2013)
  • Author(s): Takayuki Chikata, Jonathan M Carlson, Yoshiko Tamura, Mohamed Ali Borghan, Takuya Naruto, Masao Hashimoto, Hayato Murakoshi, Simon Mallal, Mina John, Hiroyuki Gatanaga, Shinichi Oka, Zabrina L. Brumme and Masafumi Takiguchi
  • Organizer: AIDS Vaccine 2013
  • Place of Presentation: Barcelona, Spain
• [Presentation] 日本人HIV-1感染者で見られるHIV-1増殖抑制能に関与する細胞傷害性T細胞 (2013)
  • Author(s): 村越 勇人
  • Organizer: 第27回日本エイズ学会学術集会・総会
  • Place of Presentation: 熊本市国際交流会館、市民会館崇城大学ホール/熊本市民会館（熊本県熊本市）
  • Invited
• [Presentation] 日本人と白人におけるHIV-1サブタイプBのHLA-Associated Polymorphismの比較解析 (2013)
  • 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, Simon Mallal, Mina John, 潟永 博之, 岡 慎一, Zabrina L Brumme, 滝口 雅文
  • Organizer: 第27回日本エイズ学会学術集会・総会
  • Place of Presentation: 熊本市国際交流会館、市民会館崇城大学ホール/熊本市民会館（熊本県熊本市）
• [Presentation] Establishment of a cohort of treatment-naive patients chronically infected with HIV-1 in Hanoi (2013)
  • Author(s): Tran Van Giang, Tomohiro Akahoshi, Hayato Murakoshi, Nozomi Kuse, Madoka Koyanagi, Takayuki Chikata, Yoshiko Tamura, Nguyen T. Hoai Dung, Nguyen Vu Trung, Junko Tanuma, Keiko Sakai, Shinichi Oka, Nguyen Van Kinh and Masafumi Takiguchi
  • Organizer: 第27回日本エイズ学会学術集会・総会
  • Place of Presentation: 熊本市国際交流会館、市民会館崇城大学ホール/熊本市民会館（熊本県熊本市）
• [Presentation] Effect of drug resistant mutations on HIV-1-specific CTL recognition (2013)
  • Author(s): Mohammad Arif Rahman, Nozomi Kuse, Hayato Murakoshi, Takayuki Chikata, Hiroyuki Gatanaga, Shinichi Oka and Masafumi Takiguchi
  • Organizer: 第27回日本エイズ学会学術集会・総会
  • Place of Presentation: 熊本市国際交流会館、市民会館崇城大学ホール/熊本市民会館（熊本県熊本市）
• [Presentation] Synergistic CTL responses effect on viraemia control of HIV-1 infection in Japanese individuals carrying HLA-B*35:01 allele associated with rapid disease progression (2013)
  • Author(s): Madoka Koyanagi, Hayato Murakoshi and Masafumi Takiguchi
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉県千葉市）
• [Presentation] Control of HIV-1 by HIV-1-specific CD8+ T cells in chronically HIV-1-infected Japanese individuals (2013)
  • Author(s): Hayato Murakoshi, Madoka Koyanagi and Masafumi Takiguchi
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉県千葉市）
• [Presentation] Cross-clade CD8+ T cell responses in chronically HIV-1 clade A/E-infected individuals (2013)
  • Author(s): Koji Watanabe, Hayato Murakoshi, Madoka Koyanagi, Takayuki Chikata and Masafumi Takiguchi
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉県千葉市）
• [Presentation] Reversion of a CTL escape mutation by escape mutant-specific CTLs (2013)
  • Author(s): Tomohiro Akahoshi, Hayato Murakoshi and Masafumi Takiguchi
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉県千葉市）
• [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ホームページ
  • URL: http://www.caids.kumamoto-u.ac.jp/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ホームページ
  • URL: http://www.caids.kumamoto-u.ac.jp/data/takiguchi/default.html