Study on HIV-1-specific CD4+ T cells that can control HIV-1 replication.

• Project/Area Number: 16K19614
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Infectious disease medicine
• Research Institution: Kumamoto University
• Principal Investigator: CHIKATA TAKAYUKI 熊本大学, エイズ学研究センター, 研究員 (60749711)
• Research Collaborator: GATANAGA Hiroyuki
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: HIV-1特異的CD4陽性T細胞 / Gag / HIV-1 / HIV-1特異的CD4T細胞 / Gag領域 / オーバーラップドペプチド / 感染症 / 免疫学 / ウイルス

Outline of Final Research Achievements

To clarify and identify of HIV-1-specific CD4+ T cells that contributed to suppression of HIV-1 replication, we analyzed the specific CD4+ T cell responses using Gag, Pol, Nef overlapping 17-mer peptides and its pools in 394 chronically HIV-1 clade B-infected Japanese individuals. We found that the T cell responders to the 3 peptide pools, Gag3, Gag4, and Pol18, had lower plasma viral load that the non-responders, and total magnitude of their responses were significantly correlated with lower plasma viral load. However, we could not establish Gag3, Gag4, and Pol18-specific CD4+ T cells form the responders. In contrast of them, we finally succeeded to establish the CD4+ T cell clones specific for a single 17mer peptide, Gag17-45, in Gag6 peptide pool from a Gag6-responder who showed high T cell response. These results gave the important knowledge and information for the development of HIV-1 vaccine.

Research Products

• [Journal Article] HLA Class I-Mediated HIV-1 Control in Vietnamese Infected with HIV-1 Subtype A/E (2017)
  • Author(s): Chikata Takayuki、Tran Giang Van、Murakoshi Hayato、Akahoshi Tomohiro、Qi Ying、Naranbhai Vivek、Kuse Nozomi、Tamura Yoshiko、Koyanagi Madoka、Sakai Sachiko、et al.
  • Journal Title: Journal of Virology Volume: 92 Issue: 5
  • DOI: 10.1128/jvi.01749-17
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Control of HIV-1 by an HLA-B*52:01-C*12:02 Protective Haplotype (2017)
  • Author(s): Chikata Takayuki、Murakoshi Hayato、Koyanagi Madoka、Honda Kazutaka、Gatanaga Hiroyuki、Oka Shinichi、Takiguchi Masafumi
  • Journal Title: The Journal of Infectious Diseases Volume: 216 Issue: 11 Pages: 1415-1424
  • DOI: 10.1093/infdis/jix483
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection (2017)
  • Author(s): Gatanaga H, Brumme ZL, Adland E, Reyes-Teran G, Avila-Rios S, Mejia-Villatoro CR, Hayashida T, Chikata T, Van Tran G, Van Nguyen K, Meza RI, Palou EY, Valenzuela-Ponce H, Pascale JM, Porras-Cortes G, Manzanero M, Lee GQ, Martin JN, Carrington MN, John M, Mallal S, Poon AFY, Goulder P, Takiguchi M, Oka S
  • Journal Title: AIDS Volume: 31 Issue: 14 Pages: 1935-1943
  • DOI: 10.1097/qad.0000000000001575
  • Peer Reviewed / Int'l Joint Research
• [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
• [Presentation] HLA class I-mediated HIV-1 control in Vietnamese infected with HIV-1 subtype A/E (2017)
  • Author(s): Chikata T, Tran GV, Murakoshi H, Akahoshi T, Qi Y, Naranbhai V, Kuse N, Tamura Y, Koyanagi M, Sakai S, Nguyen DH, Nguyen DT, Nguyen HT, Nguyen TV, Oka S, Martin MP, Carrington M, Sakai K, Nguyen KV, Takiguchi M
  • Organizer: 18th Kumamoto AIDS Seminar
  • Int'l Joint Research
• [Presentation] Control of HIV-1 by HLA-B*52:01-restricted or C*12:02-restricted cytotoxic T lymphocytes specific for 6 epitopes in an HIV-1-infected Japanese cohort where HLA-B*57 and HLA-B*27 are very rare (2017)
  • Author(s): Takayuki Chikata, Hayato Murakoshi, Madoka Koyanagi, Kazutaka Honda, Hiroyuki Gatanaga, Shinichi Oka, and Masafumi Takiguchi
  • Organizer: IAS 2017
  • Int'l Joint Research
• [Presentation] Control of HIV-1 by an HLA-B*52:01-HLA-C*12:02 protective haplotype (2017)
  • Author(s): Takayuki Chikata, Hayato Murakoshi, Madoka Koyanagi, Masafumi Takiguchi
  • Organizer: 第46回日本免疫学会学術集会
• [Presentation] 日本人およびベトナム人HIV-1感染者の病態進行の抑制に関与する細胞傷害性T細胞 (2017)
  • Author(s): 近田 貴敬
  • Organizer: 第31回日本エイズ学会学術集会・総会
  • 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アリルおよびHLA関連HIV-1多型のエイズ病態進行に及ぼす影響 (2017)
  • Author(s): 近田 貴敬, Tran Van Giang, 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31回日本エイズ学会学術集会・総会
• [Presentation] Identification of a detrimental HLA haplotype and the effect of its associated HIV-1 mutations in HIV-1 subtype A/E-infected Vietnamese (2017)
  • Author(s): Takayuki Chikata, Hayato Murakoshi, Tomohiro Akahoshi, Nozomi Kuse, Yoshiko Tamura, Keiko Sakai, Masafumi Takiguchi
  • Organizer: 第65回日本ウイルス学会学術集会