Effect of CTL responses on control of HIV-1 infection in Japanese individuals carrying HLA-B*35:01

• Project/Area Number: 25870552
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Infectious disease medicine; Virology
• Research Institution: Nippon Veterinary and Life Science University (2014); Kumamoto University (2013)
• Principal Investigator: KOYANAGI Madoka 日本獣医生命科学大学, 公私立大学の部局等, 助教 (00543399)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: HIV / CTL / HLA / HIV-1

Outline of Final Research Achievements

HLA-B*35:01 allele associates with high viral load (VL) in Japanese chronically HIV-1 clade B-infected individuals. We investigated the effect of cytotoxic T cell (CTL) responses to HLA-B*35:01-restricted epitopes on the control of HIV-1 in these individuals. Each CTL response to 4 out of 16 HLA-B*35:01-restricted epitopes was significantly but weakly associated with lower VL. The magnitude and the breadth of those 4 epitopes were significantly associated with lower VL. These results indicate even if the each response showed insufficient control of HIV-1, the multiple CTL responses to HLA-B*35:01-restricted epitopes, synergistically affect on the control of HIV-1 in HLA-B*35:01+ Japanese individuals. We found 2 significant association of the presence of HLA-B*35:01 allele with mutants, however HLA-B*35:01-restricted epitopes specific CTLs show cross-reactive with mutants. Those cross-reactive and WT specific CTLs contribute to the control of WT and mutant HIV-1 replication.

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: J. Virol. Volume: 89 Issue: 10 Pages: 5330-9
  • DOI: 10.1128/jvi.00020-15
  • Peer Reviewed
• [Journal Article] Effects of protein tyrosine phosphatase-PEST are reversed by Akt in T cells (2014)
  • Author(s): Yutaka Arimura, Kazuhiro Shimizu, Madoka Koyanagi, Junji Yagi
  • Journal Title: Cell Signal. Volume: 26 Issue: 12 Pages: 2721-9
  • DOI: 10.1016/j.cellsig.2014.08.014
  • Peer Reviewed
• [Journal Article] HIV subtype influences HLA-B*07:02-associated HIV disease outcome (2014)
  • Author(s): Henrik Kloverpris, Emily Adland, Madoka Koyanagi, Anette Stryhn, Mikkel Harndahl, Philippa C Matthews, Roger Shapiro, Bruce Walker, Thumbi Ndung'u, Christian Brander, Masafumi Takiguchi, Soren Buus, and Philip JR Goulder
  • Journal Title: AIDS Research and Human Retroviruses Volume: 30 Pages: 468-75
  • 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: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
• [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: 15th KUMAMOTO AIDS Seminar
  • Place of Presentation: 熊本
  • Year and Date: 2014-10-01 – 2014-10-03
• [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: 15th KUMAMOTO AIDS Seminar
  • Place of Presentation: 熊本
  • Year and Date: 2014-10-01 – 2014-10-03
• [Presentation] Identification of HLA-associated HIV-1subtype A/E polymorphism in a Vietnamese cohort (2014)
  • Author(s): Tran Van Giang, Takayuki Chikata, Yoshiko Tamura, Tomohiro Akahoshi, Hayato Murakoshi, Nozomi Kuse, Madoka Koyanagi, Shinichi Oka, Keiko Sakai, Nguyen Van Kinh, and Masafumi Takiguchi
  • Organizer: 15th KUMAMOTO AIDS Seminar
  • Place of Presentation: 熊本
  • Year and Date: 2014-10-01 – 2014-10-03
• [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): ayato 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] Synergistic effect of a combination of CTL response 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, Tomohiro Akahoshi, Takayuki Chikata, Hiroyuki Gatanaga, Shinichi Oka and Masafumi Takiguchi
  • Organizer: 14th KUMAMOTO AIDS Seminar
  • Place of Presentation: Aso Resort Grandvrio Hotel, Kumamoto, Japan
• [Presentation] Control of HIV-1 by HIV-1 immunodominant epitope-specific CD8+ T cells in chronically HIV-1-infected Japanese individuals (2013)
  • Author(s): Hayato Murakoshi, Madoka Koyanagi, Hiroyuki Gatanaga, Takuya Naruto, Shinichi Oka and Masafumi Takiguchi
  • Organizer: 14th KUMAMOTO AIDS Seminar
  • Place of Presentation: Aso Resort Grandvrio Hotel, Kumamoto, Japan
• [Presentation] Cross-clade CD8+ T cell responses in chronically HIV-1 clade A/E-infected individuals (2013)
  • Author(s): Koji Watanabe, Hayato Murakoshi, Yoshiko Tamura, Madoka Koyanagi, Rie Maruyama, Takayuki Chikata, Hiroyuki Gatanaga, Shinichi Oka and Masafumi Takiguchi
  • Organizer: 14th KUMAMOTO AIDS Seminar
  • Place of Presentation: Aso Resort Grandvrio Hotel, Kumamoto, Japan
• [Presentation] Inhibition of human NK cell function by an HLA-Cw*12:02-restricted HIV-1 CTL epitope peptide and its escape mutant peptide (2013)
  • Author(s): Zhansong Lin, Madoka Koyanagi and Masafumi Takiguchi
  • Organizer: 14th KUMAMOTO AIDS Seminar
  • Place of Presentation: Aso Resort Grandvrio Hotel, Kumamoto, Japan
• [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: 14th KUMAMOTO AIDS Seminar
  • Place of Presentation: Aso Resort Grandvrio Hotel, Kumamoto, Japan
• [Presentation] Effect of protease inhibitor- and integrase inhibitor-resistant mutations on HIV-1-specific CTL recognition (2013)
  • Author(s): Mohammad Arif Rahman, Nozomi Kuse, Hayato Murakoshi, Madoka Koyanagi, Hiroyuki Gatanaga, Shinichi Oka and Masafumi Takiguchi
  • Organizer: 14th KUMAMOTO AIDS Seminar
  • Place of Presentation: Aso Resort Grandvrio Hotel, Kumamoto, Japan
• [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: 市民会館 崇城大学ホール 熊本
• [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
• [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
• [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
• [Presentation] Inhibition of human NK cell function by an HLA-Cw*12:02-restricted HIV-1 CTL epitope peptide and its escape mutant peptide (2013)
  • Author(s): Zhansong Lin, 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