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Pathogenesis and Control of AIDS

Research Project

Project/Area Number 07277101
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionThe University of Tokyo

Principal Investigator

NAGAI Yoshiyuki  Institute of Medical Science, The University of Tokyo, Professor, 医科学研究所, 教授 (20022874)

Co-Investigator(Kenkyū-buntansha) HAYAMI Masanori  Institute for Virus Research, Kyoto University, Professor, ウイルス研究所, 教授 (40072946)
UCHIYAMA Takashi  Graduate School of Medicine, Kyoto University, Professor, 大学院・医学研究科, 教授 (80151900)
ADACHI Akio  School of Medicine, University of Tokushima, Professor, 医学部, 教授 (90127043)
YAMAMOTO Naoki  School of Medicine, Tokyo Medical and Dental University, Professor, 医学部, 教授 (00094053)
塩田 達雄  東京大学, 医科学研究所, 助教授 (00187329)
長澤 丘司  大阪府立母子保健総合医療センター研究所, 主任研究員 (80281690)
松下 修三  熊本大学, 医学部, 助手 (00199788)
生田 和良  北海道大学, 免疫科学研究所, 教授 (60127181)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥48,900,000 (Direct Cost: ¥48,900,000)
Fiscal Year 1998: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1997: ¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 1996: ¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 1995: ¥16,900,000 (Direct Cost: ¥16,900,000)
KeywordsHIV replication / AIDS pathogenesis / Viral genome / host factors / Human genome / anti HIV response / animal model / antiviral drugs / HIV / エイズ / ケモカイン / 化学療法 / ワクチン / HIV-1 / 細胞侵入 / 多型性 / ケモカイン受容体 / Th1 / Th2 / hPBL / SCIDマウス / 複製制御 / ウイルス病原性 / 免疫応答
Research Abstract

This project aimed to understand the mechanism of HIV replication in cells, model animals and humans, clarify the nature of host response to HIV infection and develop strategies for controlling HIV infection and AIDS pathogenesis. Over 80 researchers participated in this project, which comprised of five subthemes ; 1) Mechanism of HIV replication, 2) Virological basis of pathogenesis, 3) Immunological basis of pathogenesis, 4) Development of animal models and 5) Control of infection and pathogenesis. Their researches in three years period were able to reveal novel features of interactions of viral proteins with cellular components in HIV life cycle and identify viral genome changes, host proteins and genetic polymorphism that were likely specific for or associated with disease progression. Outcomes of the research also included the identification cytotoxic T cell epitopes crucial for antiviral state and development of animal models such as the trasgenic and SCID/hu mice and the monkey model, which allowed evaluation of HIV infection and pathogenesis. Efforts were also made to design and develop therapeutic compounds for AIDS. Several novel candidate compounds of high potential were created. These outcomes represent a significant contribution to the understanding and control of HIV/AIDS pathogenesis. Important research topics in future are further clarification of genetic and immunological background underlying susceptibility/resistance and disease progression by analyzing high risk/uninfected populations as well as long term nonprogressors. It is also important to learn how once destroyed immunological functions would be reconstructed in AIDS patients during highly active antiretroviral therapy.

Report

(5 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] T.Shioda 他: "In vivo sequence variability of human immunodeficiency virus type 1(HIV-1) envelope gp120: Association of V2 extension with slow disease progression."J.Virol.. 71. 4871-4881 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Shioda 他: "Anti-HIV-1 and chemotactic activities of human SDF-1 α and SDF-1 β are abolished by CD26/dipeptidyl peptidase IV mesiated cleavage."Proc.Natl.Acad.Sci USA. 95. 6331-6336 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Liu 他: "Polymorphism in RANTES chemokine promoter affects HIV-1 desease progression."Proc.Natl.Acad.Sci USA. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Tachibana 他: "CXCR4/fusin is not a species-specific barrier in murine cells for HIV-1 entry."J.Exp.Med.. 185. 1865-1870 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Murakami 他: "A small molecule CXCR4 inhibitor that blocks T cell-line tropic HIV-1 infection."J.Exp.Med.. 186. 1389-1393 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T. Shioda, S. Oka, X. Xin, H. Liu, R. Harukuni. A. Kurotaui, M. Fukushima, M. K. Hasan, A. Iwamoto and Y. Nagai: "In vivo sequence variability of human immunodeficiency virus type 1(HIV-1) envelope gp120 : Association of V2 extension with slow disease progression"J. Virol.. 71. 4871-4881 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T. Shioda, H. Kato, Y. Ohnishi, K. Tashito, M. Ikegawa, E. E. Nakayama, H. Hu, A. Kato, Y. Sakai, H. Liu, T. Honjo, A. Nomoto, A. Iwamoto, C. Morimoto and Y. Nagai: "Anti-HIV-1 and chemotactic activities of human SDF-1α and SDF-1β are abolished by CD26/dipeptidyl peptidase IV mediated cleavage"Proc. Natl. Acad. Sci. USA. 95. 6331-6336 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H. Liu, D. Chao, E. E. Nakayama, H. Taguchi, M. Gotoh, X. Xin, J. Takamatsu, H. Saito, Y. Ishikawa, T. Azaka, T. Juji, Y. Takebe, T. Ohishi, K. Fukutake, Y. Maruyama, S. Yashiki, S. Sonoda, T. Nakumura, Y. Nagai, A. Iwamoto and T. Shioda: "Polymorphism in RANTES chemokine promoter affects HIV-1 disease progression"Proc. Natl. Acad. Sci. USA. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K. Tachibana, T. Nakajima, A. Sato, K. Igarashi, H. Shida, H. Iizasa, N. Yoshida, O, Yoshie, T. Koshimoto and T. Nagasawa: "CXCR4/fusin is not a species-specific barrier in murine cells for HIV-1 entry"J. Exp. Med.. 185. 1865-1870 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T. Murakami, T. Nakajima, Y. Koyanagi, K. Tachibana, N. Fujii, H. Tamamura, N. Yoshida, M. Waki, A. Matsumoto, O. Yoshie, T. Kishimoto, N. Yamamoto and T. Nagasawa: "A small molecule CXCR4 inhibitor that blocks T cell-line tropic HIV-1 infection"J. Exp. Med.. 186. 1389-1393 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 永井美之 他82名: "エイズの病態と制御に関する基礎研究" 文部省特定領域研究「エイズの病態と制御に関する基礎研究」, 500 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shioda,T.: "In vivo sequence variability of human immunodeficiency virus type 1 envelope gp 120:Association of V2 extension with slow disease progression." J.Virol.71. 4871-4881 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yu,D.: "Sendai virus-based expression of HIV-1 gp 120:reinforcement by the V(-)virsion." Genes Cells. 2. 457-466 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hori,T.: "Detection and delineation of CXCR-4(fusin)as an entry and fusion cofactor for T-tropic HIV-1 entry by three different monoclonal antibodies." J.Immunol.160. 180-188 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Murakami,T.: "A small molecule CXCR4 inhibitor that blocks T cell-line tropic HIV-1 infection." J.Exp.Med.186. 1389-1393 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tachibana,K.: "CXCR4/fusin is not a species specific barrier in murine cells for HIV-1 entry." J.Exp.Med.185. 1865-1870 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Winkler,C.: "Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant." Science. 279. 389-393 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 永井 美之: "医科分子生物学(分担)" 南江堂, 501 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 永井 美之: "ウイルス・細菌感染Newファイル(編集・分担)" 羊土社, 241 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hu,H.: "Infectivities of human and other primate lentiviruses are activated by desialylation of the virion surface." J.Virol.(in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Kato,A.: "Initiation of hendai virus multiplication from transfected viral cDNA or RNA with negative or positive sense." Genes to Cells. 1. 569-579 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujii,Y.: "In vitro cytocidal effects of HIV-1 Nef on unprimed human CD4^+T cells without MHC-restriction." J.Gen.Virol.77. 2943-2951 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tanaka,Y.: "Productive and lytic infection of human CD4^+type 1 helper T cells with macrophage-tropic human immunodeficiency virus type 1." J.Virol.71. 465-470 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Koyanagi,Y.: "Primary viremia and CNS in vasion with HIV-1 in a novel hu-PBL-immunodeficient mouse." J.Virol.(in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Nagasawa,T.: "Molecular cloning and characterization of a murine pre-B-cell growth-stimulating factor/stromal cell-derived factor 1 receptor,a murine,homolog of the human immunodeficiency virus 1 entry coreceptor fusin." Proc.Natl.Acad.Sci.USA. 93. 14726-14729 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 永井美之: "医系微生物学(ヒト免疫不全ウイルス分担)" 朝倉書店, 4 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 永井美之: "医科分子生物学(HIVとエイズ分担)" 南江堂, 10 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yoshiyuki Nagai: "Virus activation by host proteinases. A pivotal role in the spread of infection, tissue tropism and pathogenicity. (Review)" Microbiol. Immunol.39. 1-9 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kishi, M.: "Naturally occurring mutations at accessory gene lead to human immunodeficiency virus type 1 persisitent infection of CD4-positive T cells." J. Virol.69. 7507-7518 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sakuragi, J.: "Generation and characterization of a host cell-dependent gag gene mutant of human immunodeficiency virus type 1." Virology. 212. 251-254 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Younong Xu: "Characterization of V3 Loop-Binding Protein(s)of Molt-4 and U937 Cells." AIDS Research and Human Retroviruses. 11. 563-570 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yamamoto, N: "The role of cytokines in the acquired immunodeficiency syndorome." Int. J. Lab. Res.25. 29-34 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shuzo Matsushita: "Neutralizing Monoclonal Antibodies against Human Immunodeficiency Virus Type 2 gp 120." J. Virol.69. 3333-3340 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 永井美之: "現代病理学大系補遺1(HIVの補助遺伝子分担)" 中山書店, 7 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 永井美之: "医系微生物学(ヒト免疫不全ウイルス分担)" 朝倉書店(印刷中),

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2019-02-15  

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