Influence of HIV protein kinetics on anti-HIV effects in HIV-specific cellular immune response

• Project/Area Number: 22590412
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: The University of Tokyo
• Principal Investigator: TACHIKAWA Ai 東京大学, 医科学研究所, 准教授 (10396880)
• Co-Investigator(Kenkyū-buntansha): MIURA Toshiyuki 長崎大学, 熱帯医学研究所, 客員教授 (00296576)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 病原性 / HIV 感染症 / CTL / 抗原提示 / エスケープ変異 / HIV感染症 / 獲得免疫応答 / HIV / 細胞性免疫 / ウイルス / 細胞性傷害性T細胞

Research Abstract

Strong and broad HIV-specific CTLs are induced against numerous targets (epitopes) during HIV infection. In this study, we demonstrates a mechanism, which generates de novo CTL epitope after one amino acid change that might result from the CTL pressure to the overlapping epitope. This novel “epitope switching” mechanism that occurs in host immunity might help the understanding of cellular immunity and CTL vaccine development.

Research Products

• [Journal Article] Generation of rejuvenated antigen-specific T cells by pluripotency reprogramming and redifferentiation (2013)
  • Author(s): Nishimura T, Kaneko S, Kawana-Tachikawa A, Tajima Y, Gotoh H, Zhu D, Nakayama K, Iriguchi S, Uemura Y, Shimizu T, Takayama N, Yamada D, Nishimura K, Ohtaka M, Watanabe N, Takahashi S, Iwamoto A, Koseki H, Nakanishi M, Eto K, Nakauchi H.
  • Journal Title: Cell Stem Cell Volume: 12 Pages: 114-26
  • Peer Reviewed
• [Journal Article] Significant Reductions in Gag-Protease-Mediated HIV-1 Replication Capacity during the Course of the Epidemic in Japan (2013)
  • Author(s): Nomura, S., N. Hosoya, Z. L. Brumme, M. A. Brockman, T. Kikuchi, M. Koga, H. Nakamura, T. Koibuchi, T. Fujii, J. M. Carlson, D. Heckerman, A. Kawana-Tachikawa, A. Iwamoto, and T. Miura.
  • Journal Title: J Virol Volume: 87 Issue: 3 Pages: 1465-76
  • DOI: 10.1128/jvi.02122-12
  • Peer Reviewed
• [Journal Article] Improved neutralizing antibody response in the second season after a single dose of pandemic (H1N1) 2009 influenza vaccine in HIV-1-positive adults (2012)
  • Author(s): Kikuchi T, Iwatsuki-Horimoto K, Adachi E, Koga M, Nakamura H, Hosoya N, Kawana-Tachikawa A, Koibuchi T, Miura T, Fujii T, Kawaoka Y, Iwamoto A.
  • Journal Title: Vaccine Volume: 30 Issue: 26 Pages: 3819-23
  • DOI: 10.1016/j.vaccine.2012.03.083
  • Peer Reviewed
• [Journal Article] Imbalanced production of cytokines by T cells associates with the activation/exhaustion status of memory T cells in chronic HIV Type 1 infection (2012)
  • Author(s): Nakayama K, Nakamura H, Koga M, Koibuchi T, Fujii T, Miura T, Iwamoto A, Kawana-Tachikawa A.
  • Journal Title: AIDS Res Hum Retroviruses Volume: 28 Issue: 7 Pages: 702-14
  • DOI: 10.1089/aid.2011.0073
  • Peer Reviewed
• [Journal Article] Long-term successful control of super-multidrug-resistant human immunodeficiency virus type 1 infection by a novel combination therapy of raltegravir,etravirine, and boosted-darunavir (2011)
  • Author(s): Nakamura H, Miyazaki N, Hosoya N, Koga M, Odawara T, Kikuchi T, Koibuchi T, Kawana-Tachikawa A, Fujii T, Miura T, Iwamoto A.
  • Journal Title: J Infect Chemother Volume: 17 Pages: 105-10
  • NAID: 10027816880
  • Peer Reviewed
• [Journal Article] Long-term successful control of super-multidrug-resistand human immunodeficiency virus type 1 infection by a novel combination therapy of raltegravir, etravirine, and boosted-darunavir (2011)
  • Author(s): Nakamura H, Miyazaki N, Hosoya N, Koga M, Odawara T, Kikuchi T, Koibuchi T, Kawana-Tachikawa A, Fujii T, Miura T, Iwamoto A
  • Journal Title: Journal of Infection Chemotherapy and chemotherapy Volume: 17 Pages: 105-110
  • Peer Reviewed
• [Journal Article] HIV-1 tropism (2010)
  • Author(s): Iwamoto A, Hosoya N, Kawana-TachikawaA.
  • Journal Title: Protein Cell Volume: 1 Issue: 6 Pages: 510-3
  • DOI: 10.1007/s13238-010-0066-2
  • Peer Reviewed
• [Journal Article] Novel immunodominant peptide presentation strategy: a featured HLA-A*2402 restricted CTL-epitope stabilized by intra-chain hudrogen-bonds from SARS-CoV nucleocapsid protein (2010)
  • Author(s): Liu J, Wu P, Gao F, Qi J, Kawana-Tachikawa A, Xie J, Vavricka CJ, Iwamoto A, Li T, Gao GF.
  • Journal Title: J Virol Volume: 84 Issue: 22 Pages: 11849-57
  • DOI: 10.1128/jvi.01464-10
  • Peer Reviewed
• [Journal Article] Changes in impact of HLA class I allele expression on HIV-1 plasma virus loads at a population level over time (2010)
  • Author(s): Koga M, Kawana-Tachikawa A, Heckerman D, Odawara T, Nakamura H, Koibuhi T, Fujii T, Miura T, Iwamoto A.
  • Journal Title: MicrobiolImmunol Volume: 54 Issue: 4 Pages: 196-205
  • DOI: 10.1111/j.1348-0421.2010.00206.x
  • NAID: 10029544438
  • Peer Reviewed
• [Journal Article] Changes in impact of HLA class I allele expression on HIV-1 plasma virus loads at a population level over time. (2010)
  • Author(s): Koga M.
  • Journal Title: Microbiol Immunol. Volume: 54 Pages: 196-205
  • Peer Reviewed
• [Journal Article] Influence of polymorphism in dendritic cell-specific intercellular adhesion molecul e-3-grbbing nonintegrin-related (DC-SIGNR) gene on HIV-1 trans-infection. (2010)
  • Author(s): Zhu D.
  • Journal Title: Biochem Biophys Res Commun. Volume: 393 Pages: 598-602
  • Peer Reviewed
• [Journal Article] HIV-1 tropism (2010)
  • Author(s): Iwamoto A.
  • Journal Title: Protein Cell Volume: 1 Pages: 510-513
  • Peer Reviewed
• [Journal Article] Imbalanced production of cyotokines by T cells associates with the activation/exhaust ion status of memory T cells in chronic HIV type 1 infection
  • Author(s): Nakayama K, Nakamura H, Koga M, Koibuchi T, Fujii T, Miura T, Iwamoto A, Kawana-Tachikawa A
  • Journal Title: AIDS Research and Human Retroviruses Volume: (印刷中)
  • Peer Reviewed
• [Presentation] Impact of an amino acid change within overlapping CTL epiotpes in HIV-1 infection. Keystone symposia (2013)
  • Author(s): Han Chungyong, Shimizu A, Zhu D, Kawana-Tachikawa A, Iwamoto A.
  • Organizer: HIV Vaccines
  • Place of Presentation: Keystone Colorado, USA
• [Presentation] Prolonged preservation of HIV-specific cellular immunity in recently HIV-infected individuals receiving Maraviroc intensified HAART. (2013)
  • Author(s): Kawana-Tachikawa A, Llibre JM, Bravo I, Escrig R, Mothe B, Miro JM, Gatell JM, Iwamoto A, Clotet B, Brander C.
  • Organizer: 20th conference on retroviruses and opportunistic infections
  • Place of Presentation: Atlanta, USA
• [Presentation] Mechanisms underlying disruption of T cell immunity during chronic HIV-1 infection. The 2nd Joint Global COE Symposium of the IMSUT & RCAST Global COE, The University of Tokyo and Chiba University Global COE "Current and Future Trends in Genome-based Immunity (2013)
  • Author(s): Kawana-Tachikawa A.
  • Organizer: Infection and Cancer
  • Place of Presentation: Tokyo
• [Presentation] Impact of an amino acid change within overlapping CTL epitopes in HIV-1 infection (2013)
  • Author(s): Han C
  • Organizer: Keystone symposia, HIV Vaccines
  • Place of Presentation: Keystone, USA
• [Presentation] Mechanisms underlying disruption of T cell immunity during chronic HIV-1 infection (2013)
  • Author(s): Kawana-Tachikawa A
  • Organizer: The 2nd joint global COE sympoisum of the IMSUT & RCAST global COE, The university of Tokyo and Chiba university global COE "Current and future trends in genome-based immunity, infection and cancer"
  • Place of Presentation: 東京ステーションコンファレンス（東京都）
  • Invited
• [Presentation] Anti-APOBEC3G activity of HIV-1 Vifprotein from elite controllers is attenuated compared to those from untreated chronic progressors of those from individuals with acute infection. (2012)
  • Author(s): Kikuchi T, Iwabu Y, Kawana-Tachikawa A, Koga M, Nomura S, Hosoya N, Brumme ZL, Heiko J, Kelleher AD, Markowitz M, Pereyra F, Trocha A, Walker BD, Iwamoto A, Tokunaga K, Miura T.
  • Organizer: XIX International AIDS Conference
  • Place of Presentation: Washington DC, USA.
• [Presentation] Development of a HIV-1 phenotypic tropism assay using dual split protein (DSP)-mediated membrane fusion detection system". (2012)
  • Author(s): Hosoya N. Teeranaipong P,Kawana-Tachikawa A, Kondo N, Hoshino H, Matsuda Z, Iwamoto A.
  • Organizer: 1st Asian Conference on Hepatitis B and C, HIV and Influenza
  • Place of Presentation: Beijing, China
• [Presentation] HIV-1elitecontrollerにおけるHIV-1Vifの抗APOBEC3G活性の低下 (2012)
  • Author(s): 菊地正、岩部幸枝、立川(川名)愛、古賀道子、野村滋、細谷紀彰、BrummeZL,HeikoJ,KelleherAD,MarkowitzM,PereyraF,TrochaA,WalkerBD,岩本愛吉、徳永研三、三浦聡之.
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
• [Presentation] 感染早期でのHAART 開始時における MaravirocによるHAART 増強の T細胞に与える影響 (2012)
  • Author(s): 立 川(川名)愛 、Beatriz Mothe-Pujadas, Marta Massanella, Josep M Libre, Bonaventura Clotet, 岩 本 愛 吉 , Christian Brander.
  • Organizer: 第26回日本エイズ学会学術集会
  • Place of Presentation: 横浜
• [Presentation] HIV感染者におけるパンデミック2009(H1N1)インフルエンザワクチンの初回接種前後と2年目の接種前後の中和抗体価の推移. (2012)
  • Author(s): 菊地正、岩附研子、安達英輔、古賀道子、中村仁美、立川愛、鯉渕智彦、藤井毅、河岡義裕、岩本愛吉.
  • Organizer: 第12回東京大学生命科学シンポジウム
  • Place of Presentation: 東京
• [Presentation] 慢性感染症としてのHIV感染症の免疫学「HIV感染慢性期におけるT細胞の免疫病態」 (2011)
  • Author(s): 立川(川名)愛
  • Organizer: 第25回に本エイズ学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-30
• [Presentation] Replication capacities of chimeric NL4-3 encoding gag-protease from modern HIV-1 isolates are significantly reduced compared to those derived from isolates in the early days of epidemic in Japan (2011)
  • Author(s): Nomura S, Hosoya N, Kikuchi T, Koga M, Nakamura H, Koibuchi T, Fujii T, Kawana-Tachikawa A, Iwamoto A, Miura T
  • Organizer: 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention
  • Place of Presentation: Rome, Italy
  • Year and Date: 2011-07-01
• [Presentation] Replication capacities of chimeric NL4-3 encoding gag-protease from modern HIV-1 isolates are significantly reduced compared to those derived from isolates in the early days of epidemic in Japan (2011)
  • Author(s): Nomura S, Hosoya N, Kikuchi T, Koga M, Nakamura H, Koibuchi T, Fujii T, Kawana-Tachikawa A, Iwamoto A, Miura T.
  • Organizer: 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention
  • Place of Presentation: Rome Italy
• [Presentation] Induction and maintenance of neutralizing antibodies after single dose of non-adjuvanted split 2009 pandemic H1N1 influenza A vaccine in HIV-1 positive population. (2011)
  • Author(s): Kikuchi T, Iwatsuki-Horimoto K, Adachi E, Imai K, Shimizu S, Miyazaki N, Koga M, Nakamura H, Kawana-Tachikawa A, Koibuchi T, Miura T, Fujii T, Kawaoka Y, Iwamoto A.
  • Organizer: 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention
  • Place of Presentation: Rome Italy
• [Presentation] HIV感染慢性期におけるT細胞の免疫病態 (2011)
  • Author(s): 立川(川名)愛
  • Organizer: 第25回日本エイズ学会学術集会
  • Place of Presentation: 東京
• [Presentation] 無症候慢性HIV-1陽性者由来gag-proteaseを発現するキメラNL4-3ウイルス複製能の患者初診年による変化. (2011)
  • Author(s): 野村滋,菊地正,細谷紀彰,古賀道子,中村仁美,鯉渕智彦,藤井毅,立川愛,岩本愛吉,三浦聡之
  • Organizer: 第25回日本エイズ学会学術集会
  • Place of Presentation: 東京
• [Presentation] HIV-1サブタイプ未同定の検体を用いた配列特異的オリゴプローブによる薬剤耐性変異の検出. (2011)
  • Author(s): 谷麗君、細谷紀彰、立川(川名)愛、中村仁美、古賀道子、松下正毅、BiyanLu、三浦聡之、岩本愛吉.
  • Organizer: 第25回日本エイズ学会学術集会
  • Place of Presentation: 東京
• [Presentation] T ell activation and exhaustion associates with skewed cytokines/chemokines production in chronic HIV-1 infection. (2010)
  • Author(s): Nakayama K.
  • Organizer: 14^<th> International Congress of Immunology.
  • Year and Date: 2010-08-26
• [Presentation] HIV-1 viral burden has an impact on Th1-and Th17-related cytokines/chemokines production of T cells. (2010)
  • Author(s): Nakayama K.
  • Organizer: 18^<th> International AIDS Conference.
  • Place of Presentation: ウイーン、オーストリア
  • Year and Date: 2010-07-22
• [Presentation] Development of a PCR-SSOP-Liminex Assay for HIV-1 Drug Resistance. Session IV: Virology, Novel Therapies, and New Technologies. (2010)
  • Author(s): Gu L, Kawana-Tachikawa A, Shiino T, Hosoya N, Nunoya J, Koibuchi T, Fujii T, Miura T, Matsushita M, Sugiura W, and Iwamoto A.
  • Organizer: 24th Joint Meeting of the AIDS Panels, United States-Japan Cooperative Medical Science Program. HIV Resistance
  • Place of Presentation: Asia. Grand Copthorne Hotel, Singapore
• [Presentation] Novel HIV-1 Phenotypic Tropism Assay without Psuedotyoed Virions. Session IV: Virology, Novel Therapies, and New Technologies.24th Joint Meeting of the AIDS Panels,United States-Japan Cooperative Medical Science Program (2010)
  • Author(s): Teeranaipong P, Hosoya N, Kawana-Tachikawa A. Kondo N, Hoshino H, Matsuda Z, and Iwamoto A.
  • Organizer: HIV Resistance
  • Place of Presentation: Asia. Grand Copthorne Hotel, Sigapore
• [Presentation] T ell activation and exhaustion associates with skewed cytokines/chemokines production in chronic HIV-1 infection. (2010)
  • Author(s): Nakayama K, Kawana-Tachikawa A, Nakamura H, Miura T, Fujii T, Koibuchi T, Iwamoto A.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe, Japan
• [Presentation] HIV-1 viral burden has an impact on Th1- and Th17-related cytokines/chemokines production of T cells. (2010)
  • Author(s): Nakayama K, Kawana-Tachikawa A, Nakamura H, Miura T, Fujii T, Koibuchi T, Iwamoto A.
  • Organizer: 18th International AIDS Conference
  • Place of Presentation: Vienna, Austria
• [Remarks]
  • URL: http://www.idimsut.jp/
• [Remarks]
  • URL: http://www.idimsut.jp/