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Basic Research for AIDS control A02 ; Pathophysiology and immunology of HIV-1 infection

Research Project

Project/Area Number 10180102
Research Category

Grant-in-Aid for Scientific Research on Priority Areas (A)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

UCHIYAMA Takashi  Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (80151900)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Hidemi  Nippon Medical School, Professor, 医学部, 教授 (40221361)
KIYONO Hiroshi  Osaka University, Research Institute for Microbial Diseases, Professor, 微生物病研究所, 教授 (10271032)
NAGASAWA Takashi  Kyoto University, Institute for Frontier Medical Sciences, Professor, 再生医学研究所, 教授 (80281690)
YOSHIE Osamu  Kinki University School of Medicine, Professor, 医学部, 教授 (10166910)
TAKIGUCHI Masafumi  Kumamoto University, Center for AIDS Research, Professor, エイズ学研究センター, 教授 (00183450)
小柳 義夫  東北大学, 医学系研究科, 教授 (80215417)
Project Period (FY) 1998 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥226,100,000 (Direct Cost: ¥226,100,000)
Fiscal Year 2001: ¥54,200,000 (Direct Cost: ¥54,200,000)
Fiscal Year 2000: ¥51,300,000 (Direct Cost: ¥51,300,000)
Fiscal Year 1999: ¥51,300,000 (Direct Cost: ¥51,300,000)
Fiscal Year 1998: ¥69,300,000 (Direct Cost: ¥69,300,000)
KeywordsHIV-1 / AIDS / Pathophysiology / Immune response / AIDS Control / Chemokine / Chemokine Receptor / dendritic cells / mucosol immunity / HIV / gp120 / 粘膜免疫 / V3ループ / エイズワクチン
Research Abstract

We have been worked mainly on chemokine/chemokine receptor system in HIV-1 infection and HIV-1-specific CTL, and got many results as described below. Uchiyama reported that natural alpha interferon-producing cells, which was a precursor of certain dendritic cell subsets and played a crucial role in an innate immune response, could be infected with HIV-1 and produce a large amount of alpha interferon in response to HIV-1 infection to differentiate into dendritic cells. Nagasawa identified a subset of the most immature precursor B cells and showed that SDF-1 is essential for the development of this cell subset using various knockout mice. Yoshie analyzed the role of immune chemokine constitutively expressed in lymphoid organs in HIV-1 infection. He also analyzed the suppressive effect of P2G-SDF-1-Fc chimeric protein on HIV-1 infection. Kiyono reported that immunization with gp160-fusogenic liposome through nasal mucosa induced the neutralizing antibodies response in not only wild type mice but also IFN-γ-knockout mice or IL-4-knockout mice, indicating a possible implication of this vaccine as a therapeutic vaccine. Takahashi reported detailed mechanism of CTL response to HIV-1 infection. Takizawa found that HIV-1-specific CD8(+) CTL expressed CCR5 on their surfaces and migrated by this ligand, indicating that these chemikines might be involved in the induction of Th1 response.

Report

(5 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (49 results)

All Other

All Publications (49 results)

  • [Publications] Yonezawa A.: "Natural Alpha Interferon-Producing Cells Respond to Human Immunodeficiency Virus Type 1 with Alpha Interferon Production and Maturation into Dendritic Cells"J.Virol.. 77(6). 3777-3784 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshie O.: "Chemokines in immunity"Advances in Immunology. 78. 57-110 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Egawa T.: "The earliest stages of B cell development require a chemokine stromal cell-derived factor/pre-B-cell growth stimulating factor"Immunity. 15. 323-334 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kunisawa, J: "Novel antigen delivery system using fusogenic liposome for the induction of mucosal and systemic immune responses"J.Immunol.. 167. 1406-1412 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takahashi M.: "Rapid induction of apoptosis in CD8+ HIV-1 envelope-specific murine CTLs by short exposure to antigenic peptide"J.Immunol.. 169(11). 6588-6593 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fukada K.: "Functional expression of the chemokine receptor CCR5 on virus epitope-specific memory and effector CD8+ T ceels"J.Immunol.. 168. 2225-2232 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yonezawa A. et al: "Natural Alpha Interferon-Producing Cells Respond to Human Immunodeficiency Virus Type 1 with Alpha Interferon Production and Maturation into Dendritic Cells"J. Virol.. 77(6). 3777-3784 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yonezawa A. et al: "Replacement of the V3 Region of gp120 with SDF-1 Preserves the Infectivity of T-Cell Line-Tropic Human Immunodeficiency Virus Type 1"J. Virol.. 75(9). 4258-4267 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ichiyama K. et al: "A duodenally absorbable CXC chemokine receptor 4 antagonist, KRH-1636, exhibits a potent and selective anti-HIV-1 activity"Proc. Natl. Acad. Sci. USA. 100(7). 4185-4190 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miura Y. et al: "Tumor necrosis factor-related apoptosis-inducing ligand induces neuronal death in a murine model of HIV central nervous system infection"Proc. Natl. Acad. Sci. USA. 100(5). 2777-2782 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] KimuraT. et al: "Reconstitution of spontaneous neutralizing antibody response against autologous human immunodeficiency virus during highly active antiretroviral therapy"J. Infect. Dis.. 185(1). 53-60 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wang FX. et al: "Emergence of autologous neutralization-resistant variants from preexisting human immunodeficiency virus (HIV) quasi species during virus rebound in HIV type 1-infected patients undergoing highly active antiretroviral therapy"J. Infect. Dis.. 185(5). 608-617 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Gatanada H. et al: "Amino acid substitutions in non-cleavage sites of the gag region are indispensable for high level HIV-1 resistance to protease inhibitors"J. Biol. Chem.. 277. 5952-5961 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miyakawa T. et al: "Identification of amino acid residues critical for LD78β (a variant of human macrophage inflammatory protein-1 α) binding to CCR5 and inhibition of R5 HIV-1 replication"J. Biol. Chem.. 277. 4649-4655 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Egawa, T: "The earliest stages of B cell development require a chemokine stromal cell-derived factor/pre-B-cell growth stimulating factor"Immunity. 15. 323-334 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshie, O: "Chemokines in immunity"Advances in Immunology. 78. 57-110 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kunisawa, J: "Novel antigen delivery system using fusogenic liposome for the induction of mucosal and systemic immune responses"J. Immunol.. 167. 1406-1412 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hiroi, T: "HIV mucosal vaccine : nasal immunization with rBCG-V3J1 induces a long-term V3J1-peptide-specific neutralizing immunity in Th1 and Th2 deficient conditions"J. Immunol.. 167. 5862-5867 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takahashi, M: "Counter-regulation cytotoxic activity and cytokine production in human immunodeficiency virus(HIV)-1-specific murine CD8+ cytotoxic T lymphocytes by free antigenic peptide"Int. Immunol.. 13. 43-51 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fukada, H: "Functional Expression of the Chemokine Receptor CCR5 on Virus Epitope-Specific Memory and Effector CD8+ T Cells"J. Immunol.. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Yonezawa,A: "Replacement of V3 region of gp120 with SDF-1 preserves the infectivity of T-tropic human immunodeficiency virus type 1."J Virol. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Nagasawa,T: "A chemokine, SDF-1/PBSF, and its receptor, CXCR4 as mediators of hematopoiesis."International Journal of Hematology. 72. 408-408 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hiroi,T: "Interleukin 15 and IL-15R selectively regulate differentiation of common mucosal immune system-independent B-1 cells for IgA responses."J.Immunol.. 165. 4329-4337 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takahashi,M: "Counter-regulation of cytolytic activity and cytokine production in human immunodeficiency virus (HIV)-1-specific murine CD8+ cytotoxic T lymphocytes by free antigenic peptide."Int.Immunol.. 13. 43-51 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tomiyama,H: "Expansion of HIV-1-specific CD28^-CD45RA^-CD8^+ T cells in chronically HIV-1 infected individuals."AIDS.. 14. 2049-2051 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Zlotnik,A: "Chemokines : a new classification system and their role in immunity."Immunity. 12. 121-127 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Isaka , Y.: "Small Amino acid changes in the V3 loop of human immunodeficiency virus type 2 determines the coreceptor usage for CXCR4 and CCR5"Virol. 264. 237-243 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nagasawa, T.: "A CXC chemokine SDF-1/PBSF : A ligand for a HIV coreceptor, CXCR4"Adv. Immunol.. 71. 211-228 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawabata, K.: "A cell-autonomous requirement for CXCR4 in long-term lymphoid and myeloid reconstitution"Proc. Natl. Acad. Sci. USA. 96. 5663-5667 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] McGhee, J. R.: "Mucosal Th1-versus Th2-type responses for antibody or cell mediated immunity to SIV rhesus macaques"J. Infect. Dise.. 179. 5480-5484 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ohashi, T.: "Role of class I major histocompatibility complex-restricted and -unrestricted suppression of human immunodeficiency virus type 1 replication CD8^+ T lymphocytes"J. Gen. Virol.. 80. 209-216 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tomiyama, H.: "Identification of Multiple HIV-1 Epitopes presented by HLA-B*5101 Molecules"Hum. Immunol.. 60. 177-186 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tomiyama, H.: "Cytotoxic T-lymphocyte recognition of HLA-B*5101-restricted HIV-1 Rev epitope which is naturally processed in HIV-1 infected cells"AIDS. 13. 861-863 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawana, A.: "Accumulation of specific amino acid substitutions in HLA-B35-restricted human immunodeficiency virus type-1 cytotoxic T lymphocyte epitopes"AIDS. Res. Hum. Retroviruses.. 12. 1099-1107 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukada, K.: "HLA-A*1101-restricted CTL recognition of HIV-1 Pol protein"AIDS. 13. 1413-1414 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukada, K.: "HLA-A*1101-restricted CTL recognition for a novel epitope derived from the HIV-1 Env protein"AIDS. 13. 2597-2599 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Suzuki, Y.: "Determinant in human immunodeficiency virus type 1 for efficient replication under cytokine induced CD4^+ T-helper 1 (Th1)-and Th2-type conditions"J Virol. 73. 316-324 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Murakami, T.: "Inhibitory mechanism of the CXCR4 antagonist T22 against human immunodeficiency virus type 1 (HIV-1) infection"J Virol. 73. 7489-7496 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ichiyama, K.: "Epitope mapping of rat neutralizing monoclonal antibody against human immunodeficiency virus type-1 by a phage peptide library : comparison with ELISA using synthetic peptides"Viral Immunol. 12. 57-66 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Maeda, N.: "Acquisition of HIV-1 resistance by β-chemokine-producing CD4+ T cells"AIDS Res Hum Retroviruses. 15. 1453-1460 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takahashi, K.: "Structural requirement for the two-step dimerization of human immunodeficiency virus type-1 genome"RNA. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Momoi, Y.: "Pertusis toxin enhances human immunodefieicncy virus-1 replication"AIDS Res Hum Retroviruses. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Chiaba, M.: "Recombinant vaccinia virus expressing an immunodominant epitope of HIV-1 envelope protein within an influenza hemagglutinin cassette predominantly prime epitope-specific CD8+ CTL"Arch. Virol.. 144. 1469-1485 (1999)

    • Related Report
      1999 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
      1998 Annual Research Report
  • [Publications] Sakaida H.: "T-tropic human immunodeficiency virus type 1 (HIV-1)-derived V3 loop peptides directly bind to CXCR-4 and inhibit T-tropic HIV-1 infection." J Virol. 72 (2). 9763-9770 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tachibana,K.: "The chomokinase receptor CXCR4 is essential for vascularization of the gastrointertinal tract" Nature. 393. 591-594 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Imaoka,I.: "Nasal Immunization of non-human primates with simian immunodeficiency virus p55gag and cholera toxin adjuvant induces Th1/Th2 help for anti-viral immunity." J.Immunol.161. 5952-5958 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Moore,I.Y.: "Identification of a novel HLA-A24-restricted CTL epitope derived from HIV-1 Gag protein." AIDS. 12. 2073-2074 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Suzuki Y: "Determinant in human immunodeficiency virus type 1 for efficient replication in cytokine induced CD4+ T helper 1 (Th1)- and Th2-type conditions." J Virol. 73. 316-324 (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2018-03-28  

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