A study of HIV-1 escape mutants selected by cellular immunity

• Project/Area Number: 20390134
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Kumamoto University
• Principal Investigator: TAKIGUCHI Masafumi Kumamoto University, エイズ学研究センター, 教授 (00183450)
• Co-Investigator(Renkei-kenkyūsha): OKA Shinichi 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)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000); Fiscal Year 2010: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2009: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2008: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: 感染防御 / ワクチン / 免疫逃避 / CTL

Research Abstract

We identified novel 3 escape mutations from HIV-1-specific CTLs. We analyzed one escape mutation of them, RT 135 mutation, and found that this mutation accumulated in 9 cohorts. In addition, we showed the accumulation of other 13 escape mutations in these cohorts. These findings demonstrated strong evidence of HIV adaptation to HLA at a population level.

Research Products

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