細胞性免疫により選択されるHIV-1逃避変異ウイルスに関する研究

• 研究課題/領域番号: 20390134
• 研究種目: 基盤研究(B)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: ウイルス学
• 研究機関: 熊本大学
• 研究代表者: 滝口 雅文 熊本大学, エイズ学研究センター, 教授 (00183450)
• 連携研究者: 岡 慎一 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)
• 研究期間 (年度): 2008 – 2010
• 研究課題ステータス: 完了 (2010年度)
• 配分額: 19,500千円 (直接経費: 15,000千円、間接経費: 4,500千円); 2010年度: 6,110千円 (直接経費: 4,700千円、間接経費: 1,410千円); 2009年度: 6,110千円 (直接経費: 4,700千円、間接経費: 1,410千円); 2008年度: 7,280千円 (直接経費: 5,600千円、間接経費: 1,680千円)
• キーワード: 感染防御 / ワクチン / 免疫逃避 / CTL

研究概要

我々が明らかにしたHIV-1エピトープに特異的なCTLを用いて、新たに3つの逃避変異を明らかにした。このうち、HLA-B*5101拘束性Pol283特異的CTLが選択する逃避エピトープの蓄積を、世界9つのコホートで解析し、その逃避変異の蓄積を明らかにした。更にこれらのコホートで、知られている13個の逃避変異の蓄積を明らかし、HIV-1がHLAに適応するように進化していることを明らかにした。

研究成果

• [雑誌論文] Effective recognition of HIV-1-infected cells by HIV-1 integrase-specific HLA-B*4002-restricted T cells. (2011)
  • 著者名/発表者名: Tamayo Watanabe, Hayato Murakoshi, Hiroyuki Gatanaga, Madoka Koyanagi, Shinichi Oka, Masafumi Takiguchi
  • 雑誌名: Microbes Infect. 13 ページ: 160-166
  • 査読あり
• [雑誌論文] Selection of escape mutant by HLA-C-restricted HIV-1 Pol-specific cytotoxic Tlymphocytes carrying strong ability to suppress HIV-1 replication. (2011)
  • 著者名/発表者名: Kazutaka Honda, Nan Zheng, Hayato Murakoshi, Masao Hashimoto, Keiko Sakai, Mohamed Ali Borghan, Takayuki Chikata, Madoka Koyanagi, Yoshiko Tamura, Hiroyuki Gatanaga, Shinichi Oka, Masafumi Takiguchi
  • 雑誌名: Eur.J.Immunol. 41 ページ: 97-106
  • 査読あり
• [雑誌論文] Selection of HLA-B57-associated Gag A146P mutant by HLA-B^*48:01-resticted Gag 140-147-specific CTLs in chronically HIV-1-infected Japanese (2011)
  • 著者名/発表者名: Naruto T., et al
  • 雑誌名: Microbes Infect. 巻: (in press)
  • 査読あり
• [雑誌論文] Selection of escape mutant by HLA-C-restricted HIV-1 Pol-specific cytotoxic T lymphocytes carrying strong ability to suppress HIV-1 replication (2011)
  • 著者名/発表者名: Honda K., et al
  • 雑誌名: Eur J Immunol. 巻: 41 ページ: 97-106
  • 査読あり
• [雑誌論文] Effective recognition of HIV-1-infected cells by HIV-1 integrase-specific HLA-B*4002-restricted T cells (2011)
  • 著者名/発表者名: Watanabe T., et al
  • 雑誌名: Microbes Infect. 巻: 13 ページ: 160-166
  • 査読あり
• [雑誌論文] Long-term control of HIV-1 in hemophiliacs carrying slow-progressing allele HLA-B*5101. (2010)
  • 著者名/発表者名: Yuka Kawashima, Nozomi Kuse, Hiroyuki Gatanaga, Takuya Naruto, Mamoru Fujiwara, Sachi Dohki, Tomohiro Akahoshi, Katsumi Maenaka, Philip Goulder, Shinichi Oka, Masafumi Takiguchi
  • 雑誌名: J.Virol. 84 ページ: 7151-7160
  • NAID: 120002754175
  • 査読あり
• [雑誌論文] Different in vivo effects of HIV-1 immunodominant epitope-specific CTLs on selection of escape mutant viruses. (2010)
  • 著者名/発表者名: Hirokazu Koizumi, Masao Hashimoto, Mamoru Fujiwara, Hayato Murakoshi, Takayuki Chikata, Mohamed Ali Borghan, Atsuko Hachiya, Yuka Kawashima, Hiroshi Takata, Takamasa Ueno, Shinichi Oka, Masafumi Takiguchi
  • 雑誌名: J.Virol. 84 ページ: 5508-5519
  • 査読あり
• [雑誌論文] Selection of escape mutation by Pol154-162-specific cytotoxic T cells among chronically HIV-1-infected HLA-B*5401-positive individuals. (2010)
  • 著者名/発表者名: Masao Hashimoto, Mitsutaka Kitano, Kazutaka Honda, Hirokazu Koizumi, Sachi Dohki, Shinichi Oka, Masafumi Takiguchi
  • 雑誌名: Hum.Immunol. 71 ページ: 123-127
  • 査読あり
• [雑誌論文] Strong ability of Nef-specific CD4+ cytotoxic T cells to suppress HIV-1 replication in HIV-1-infected CD4+ T cells and macrophages. (2009)
  • 著者名/発表者名: Nan Zheng, Mamoru Fujiwara, Takamasa Ueno, Shinichi Oka, Masafumi Takiguchi
  • 雑誌名: J.Virol. 83 ページ: 7668-7677
  • 査読あり
• [雑誌論文] Identification and characterization of 2 HIV-1 Gag immunodominant epitopes restricted by Asian HLA allele HLA-B*4801 (2009)
  • 著者名/発表者名: Hayato Murakoshi, Mitsutaka Kitano, Tomohiro Akahoshi, Yuka Kawashima, Sachi Dohki, Shinichi Oka, Masafumi Takiguchi
  • 雑誌名: Hum.Immunol. 70 ページ: 170-174
  • 査読あり
• [雑誌論文] (*equally contribution) Adaptation of HIV-1 to Human Leukocyte (2009)
  • 著者名/発表者名: Yuka Kawashima, Katja Pfafferott, John Frater, PhilipPa Matthews, Rebecca Payne, Marylyn Addo, Hiroyuki Gatanaga, Mamoru Fujiwara, Atsuko Hachiya, Hirokazu Koizumi, Nozomi Kuse, Shinichi Oka, Masafumi Takiguchi, Philip Goulder
  • 雑誌名: Antigen class I. Nature 458 ページ: 641-645
  • 査読あり
• [雑誌論文] Escape mutation selected by Gag28-36-specific cytotoxic T cells in HLA-A*2402-positive HIV-1-infected donors (2009)
  • 著者名/発表者名: Hirokazu Koizumi, Tomomi Iwatani, Junko Tanuma, Mamoru Fujiwara, Taisuke Izumi, Shinichi Oka, Masafumi Takiguchi
  • 雑誌名: Microbes Infect. 11 ページ: 198-204
  • 査読あり
• [雑誌論文] Escape mutation selected by Gag28-36-specific cytotoxic T cells in HLA-A*2402-positive HIV-1-infected donors (2009)
  • 著者名/発表者名: Hirokazu Koizumi
  • 雑誌名: Microbes and Infection 11 ページ: 198-204
  • 査読あり
• [雑誌論文] Adaptation of HIV-1 to Human Leukocyte Antigen class I (2009)
  • 著者名/発表者名: Yuka Kawashima
  • 雑誌名: Nature 458 ページ: 641-645
  • 査読あり
• [雑誌論文] Identification and characterization of 2 HIV-1 Gag immunodominant epitopes restricted by Asian HLA allele HLA-B*4801 (2009)
  • 著者名/発表者名: Hayato Murakoshi
  • 雑誌名: Human Immunology 70 ページ: 170-174
  • 査読あり
• [雑誌論文] Identification and characterization of HLA-B*5401-restricted HIV-1-Nef and Pol-specific CTL epitopes (2008)
  • 著者名/発表者名: Mitsutaka Kitano, Naoki Kobayashi, Yuka Kawashima, Tomohiro Akahoshi, Kiyoshi Nokihara, Shinichi Oka, Masafumi Takighuchi
  • 雑誌名: Microbes Infect. 10 ページ: 764-772
  • 査読あり
• [雑誌論文] HLA-A*2402-restricted HIV-1-specific cytotoxiCTLymphocytes and escape mutation after ART with structured treatment interruptions (2008)
  • 著者名/発表者名: Junko Tanuma, Mamoru Fujiwara, Katsuji Teruya, Saori Matsuoka, Hikaru Yamanaka, Hiroyuki Gatanaga, Natsuo Tachikawa, Yoshimi Kikuchi, Masafumi Takiguchi, Shinichi Oka
  • 雑誌名: Microbes Infect. 10 ページ: 689-698
  • 査読あり
• [雑誌論文] Different Ability of Escape Mutant-Specific Cytotoxic T Cells to Suppress Replication of Escape Mutant and Wild-type HIV-1 in New Hosts (2008)
  • 著者名/発表者名: Mamoru Fujiwara
  • 雑誌名: Journal of Virology 82 ページ: 138-147
  • 査読あり
• [雑誌論文] Different immunodominance of HIV-1-specific CTL epitopes among three subtypes of HLA-A*26 associated with slow progression to AIDS (2008)
  • 著者名/発表者名: Yuka Kawashima
  • 雑誌名: Biochemical and Biophysical Research Communications 366 ページ: 612-616
  • 査読あり
• [雑誌論文] Identification and characterization of HLA-B*5401-restricted HIV-1-Nef and Pol-specific CTL epitopes (2008)
  • 著者名/発表者名: Mitsutaka Kitano
  • 雑誌名: Microbes and Infection 10 ページ: 764-772
  • 査読あり
• [雑誌論文] Selection of HLA-B57-associated Gag A146P mutant by HLA-B*48:01-resticted Gag140-147-specific CTLs in chronically HIV-1-infected Japanese.
  • 著者名/発表者名: Takuya Naruto, Hayato Murakoshi, Takayuki Chikata, Madoka Koyanagi, Yuka Kawashima, Hiroyuki Gatanaga, Shinichi Oka, Masafumi Takiguchi
  • 雑誌名: Microbes Infect. In press
  • 査読あり
• [雑誌論文] Different in vivo effects of HIV-1 immunodominant epitope-specific CTLs on selection of escape mutant viruses
  • 著者名/発表者名: Koizumi H., et al.
  • 雑誌名: J Virol (in press)
  • 査読あり
• [雑誌論文] Long-term control of HIV-1 in hemophiliacs carrying slow-progressing allele HLA-B*5101
  • 著者名/発表者名: Kawashima Y., et al.
  • 雑誌名: J Virol (in press)
  • 査読あり
• [学会発表] Recognition and selection of HIV-1 escape mutations by CTL (2011)
  • 著者名/発表者名: Masafumi Takiguchi
  • 学会等名: International Symposium "Virus, host, and disease"
  • 発表場所: 京都大学芝蘭会館,京都市
  • 年月日: 2011-03-11
• [学会発表] Recognition and selection of HIV-1 escape mutations by CTL (2011)
  • 著者名/発表者名: 滝口雅文
  • 学会等名: International Symposium "Virus, host, and disease"
  • 発表場所: 京都大学芝蘭会館(京都)(招待講演)
  • 年月日: 2011-03-11
• [学会発表] HLA-Associated Viral Polymorphism in Chronically HIV-1-Infected Japanese Cohort, (2011)
  • 著者名/発表者名: Takayuki Chikata, Masao Hashimoto, Yoshiko Tamura, Takuya Naruto, Mohamed Ali Borghan, Hiroyuki Gatanaga, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: Keystone symposia-HIV Evolution, Genomics and Pathogenesis
  • 発表場所: Whistler Conference Centre, BC, Canada
• [学会発表] Keystone symposia-Protection from HIV : Targeted Intervention Strategies (2011)
  • 著者名/発表者名: Tomohiro Akahoshi, Hiroyuki Gatanaga, Shinichi Oka, Masafumi Takiguchi, Antiviral activities of HIV-1-specific T Lymphocytes cross-recognizing an escape mutation
  • 発表場所: Whistler Conference Centre, BC, Canada
• [学会発表] HLA-B*3501 is associated with different outcomes in HIV-1 according to the clade of infection (2011)
  • 著者名/発表者名: Madoka Koyanagi, Philippa C.Matthews, Hiroyuki Gatanaga, Shinichi Oka, M.Harndahl, J.Carlson, R.P.Payne, H.Kloverpris, T.Ndung'u, F.Chen, L.Riddell, G.Luzzi, S.Buus, R.Shapiro, D.Heckerman, Masafumi Takiguchi, P.Goulder
  • 学会等名: Keystone symposia-Protection from HIV : Targeted Intervention Strategies
  • 発表場所: Whistler Conference Centre, BC, Canada
• [学会発表] Comprehensive analysis of HIV-1-specific CD8+T cell responses in chronically HIV-1-infected Japanese cohort (2011)
  • 著者名/発表者名: Hayato Murakoshi, Hiroyuki Gatanaga, Madoka Koyanagi, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: Keystone symposia-Protection from HIV : Targeted Intervention Strategies
  • 発表場所: Whistler Conference Centre, BC, Canada
• [学会発表] AIDS Vaccine Development : The Present and Future The 19th Symposium on the International Medical Cooperation (2010)
  • 著者名/発表者名: Masafumi Takiguchi
  • 学会等名: Vaccine save our century
  • 発表場所: 国立国際医療研究センター,東京都
  • 年月日: 2010-11-19
• [学会発表] AIDS Vaccine Development : The Present and Future (2010)
  • 著者名/発表者名: 滝口雅文
  • 学会等名: The 19th Symposium on the International Medical Cooperation "Vaccine save our century"
  • 発表場所: 国立国際医療研究センター(東京)(招待講演)
  • 年月日: 2010-11-19
• [学会発表] Selection of HIV-1 escape mutant by HLA-C-restricted cytotoxic T Lymphocytes having a strong ability to suppress HIV-1 replication (2010)
  • 著者名/発表者名: Kazutaka Honda, N.Zheng, H.Murakoshi, M.Hashimoto, K.Sakai, M.Koyanagi, T.Chikata, Y.Tamura, M.A.Borgham, H.Gatanaga, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: AIDS Vaccine 2010
  • 発表場所: Omni Hotel at CNN Center, Atlanta, USA
• [学会発表] Selection of escape mutant by HLA-C-restricted HIV-1 Pol-specific cytotoxic T lymphocytes having a strong ability to suppress HIV-1 replication (2010)
  • 著者名/発表者名: Kazutaka Honda, N.Zheng, M.Hashimoto, K.Sakai, T.Chikata, Y.Tamura, M.A.Borgham, H.Gatanaga, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: 14th International Congress of Immunology
  • 発表場所: 神戸コンペンションセンター,神戸市
• [学会発表] Long term control of HIV-1 replication by Po1283-8-specific CTLs in HLA-B*5101+solw progressors (2010)
  • 著者名/発表者名: Nozomi Kuse, Yuka Kawashima, Hiroyuki Gatanaga, Takuya Naruto, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: 14th International Congress of Immunology
  • 発表場所: 神戸コンベンションセンター,神戸市
• [学会発表] Comprehensive analysis of escape mutation from HIV-1-specific cytotoxic T cells restricted by Asian allele HLA-B*5401 (2010)
  • 著者名/発表者名: Masao Hashimoto, Mitsutaka Kitano, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: Keystone symposia-HIV-Vaccines
  • 発表場所: Fairmont Banff Springs, AB, Canada
• [学会発表] Roles of CD4+T Cells in the Control of HIV Infection : The Victim Strikes Back (2010)
  • 著者名/発表者名: Nan Zheng, Mamoru Fujiwara, Takamasa Ueno, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: International Young Investigator Symposium 2010
  • 発表場所: グランヴイリオホテノレ,熊本県阿蘇市
• [学会発表] Selection of escape mutant by HLA-C-restricted HIV-1 Pol-specific cytotoxic T lymphocytes having a strong ability to suppress HIV-1 replication (2010)
  • 著者名/発表者名: Kazutaka Honda, N.Zheng, H.Murakoshi, M.Hashimoto, K.Sakai, T.Chikata, Y.Tamura, M.A.Borgham, H.Gatanaga, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: International Young Investigator Symposium 2010
  • 発表場所: グランヴイリオホテル,熊本県阿蘇市
• [学会発表] Comprehensive analysis of escape mutation from HIV-1-specific cytotoxic T cells restricted by Asian allele HLA-B*5401 (2010)
  • 著者名/発表者名: Masao Hashimoto, Mitsutaka Kitano, Kazutaka Honda, Hirokazu Koizumi, Sachi Dohki, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: Int.Young Investi-gator Symposium 2010
  • 発表場所: グランヴイリオホテル,熊本県阿蘇市
• [学会発表] Control of HIV-1 by HIV-1 Pol-specific CD8+ T cells in chronically HIV-1-infected Japanese cohort (2009)
  • 著者名/発表者名: Murakoshi H., et al.
  • 学会等名: AIDS Vaccine 2009
  • 発表場所: Marriott Rive Gauche Conference Center(Paris, France)
  • 年月日: 2009-10-21
• [学会発表] Control of HIV-1 by HIV-1 Pol-specific CD8+ T cells in chronically HIV-1-infected Japanese cohort (2009)
  • 著者名/発表者名: Hayato Murakoshi, Hiroyuki Gatanaga, Madoka Koyanagi, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: AIDS Vaccine 2009
  • 発表場所: Marriott Rive Gauche Conference Center, Paris
• [学会発表] HLA-B*5101 and HIV infection (2009)
  • 著者名/発表者名: Masafumi Takiguchi
  • 学会等名: 10th Kumamoto AIDS Seminar-GCOE joint International Symposium
  • 発表場所: ホテノレ日航熊本,熊本市
• [学会発表] Selection of escape mutation by Pol154-162-specific cytotoxic T cells among chronically HIV-1-infected HLA-B*5401-positive individuals (2009)
  • 著者名/発表者名: Masao Hashimoto, M.Kitano, K.Honda, Hirokazu Koizumi, Sachi Dohki, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: 10th Kumamoto AIDS Seminar-GCOE joint Int.Symposium
  • 発表場所: ホテノレ日航熊本,熊本市
• [学会発表] Control of HIV-1 by HIV-1 Pol-specific CD8+ T cell sin chronically HIV-1-infected Japanese cohort (2009)
  • 著者名/発表者名: Hayato Murakoshi, Hiroyuki Gatanaga, Madoka Koyanagi, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: 10th Kumamoto AIDS Seminar-GCOE joint International Symposium
  • 発表場所: ホテル日航熊本,熊本市
• [学会発表] Selection of escape mutant by HLA-C-restricted HIV-1-specific cytotoxic T lymphocytes having a strong ability of to suppress HIV-1 replication (2009)
  • 著者名/発表者名: Kazutaka Honda, M.Hashimoto, K.Sakai, T.Akahoshi, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: 10th Kumamoto AIDS Seminar-GCOE joint Int.Symposium
  • 発表場所: ホテル日航熊本,熊本市
• [学会発表] Competitive HIV-1 replication suppression assay : selection of HIV-1 escape mutants by HLA-B*5101-restricted Pol283-8-specific CTLs (2009)
  • 著者名/発表者名: Nozomi Kuse, Y.Kawashima, H.Gatanaga, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: 10th Kumamoto AIDS Seminar-GCOE joint Int.Symposium
  • 発表場所: ホテル日航熊本,熊本市
• [学会発表] Strong ability of Nef-specific CD4+ cytotoxic T cells to suppress HIV-1 replication in HIV-1-infected CD4+ T cells and macrophages (2009)
  • 著者名/発表者名: Nan Zheng, M.Fujiwara, T.Ueno, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: 10th Kumamoto AIDS Seminar-GCOE joint Int.Symposium
  • 発表場所: ホテル日航熊本,熊本市
• [学会発表] HIV-1-specific CD8+ T cell responses in ART-free Japanese cohort (2009)
  • 著者名/発表者名: Hayato Murakoshi, H.Gatanaga, Akiko Taki, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: Keystone symposia-HIV Immunobiology
  • 発表場所: Keystone Resort, Denver, USA
• [学会発表] A strong ability of HLA-C-restricted HIV-1-specific cytotoxic T lymphocytes to suppress HIV-1 replication and escape mutations from the CTLs (2009)
  • 著者名/発表者名: Kazutaka Honda, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: Keystone symposia-HIV Immunobiology
  • 発表場所: Keystone Resort, Denver, USA
• [学会発表] Selection of HIV-1 escape mutants from HIV-1-specific CTLs in HIV-1 replication suppression assay (2009)
  • 著者名/発表者名: Nozomi Kuse, Yuka Kawashima, Hiroyuki Gatanaga, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: Keystone symposia-HIV Immunobiology
  • 発表場所: Keystone Resort, Denver, USA
• [学会発表] Killing of HIV-1-infected CD4+ T cells and macrophages by an HIV-1 Nef-specific CD4+CTL (2008)
  • 著者名/発表者名: Nan Zheng, Mamoru Fujiwara, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: Kumamoto AIDS Seminar
  • 発表場所: グランヴィリオホテル,熊本県阿蘇市
• [学会発表] Different effects of HIV-1-specific CTLs having a strong ability to suppress HIV-1 replication on selection of escape mutant viruses (2008)
  • 著者名/発表者名: Hirokazu Koizumi, M.Fujiwara, A.Hachiya, Y.Kawashima, T.Ueno, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: Kumamoto AIDS Seminar
  • 発表場所: グランヴィリオホテル,熊本県阿蘇市
• [学会発表] Selection of escape mutant from HLA-Cw*1202-restricted cytotoxic T lymphocytes having a strong ability to suppress HIV-1 replication (2008)
  • 著者名/発表者名: Kazutaka Honda, H.Koizumi, Z.Nan, T.Akahoshi, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: Kumamoto AIDS Seminar
  • 発表場所: グランヴィリオホテル,熊本県阿蘇市
• [学会発表] Selection of HIV-1 escape mutants from HIV-1-specific CTLs in HIV-1 replication suppression assay (2008)
  • 著者名/発表者名: Nozomi Kuse, Yuka Kawashima, Masafumi Takiguchi
  • 学会等名: Kumamoto AIDS Seminar
  • 発表場所: グランヴィリオホテル,熊本県阿蘇市
• [学会発表] Identification of HLA-B*4801-restricted HIV-1-Gag epitopes (2008)
  • 著者名/発表者名: Hayato Murakoshi, Mitsutaka Kitano, Shinichi Oka, Masafumi Takiguchi
  • 学会等名: Kumamoto AIDS Seminar
  • 発表場所: グランヴィリオホテル,熊本県阿蘇市
• [備考] ホームページ等
  • URL: http://www.caids.kumamoto-u.ac.jp/data/takiguchi/default.html
• [備考]
  • URL: http://www.caids.kumamoto-u.ac.jp/data/takiguchi/default.html
• [備考]
  • URL: http://www.caids.kumamoto-u.ac.jp/data/takiguchi/default.html