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Analysis of mechanism of HIV mucosa' infection and immunity using SHIV-monkey system

Research Project

Project/Area Number 14021046
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyoto University

Principal Investigator

HAYAME Masanori  Kyoto University, Institute for Virus Research, Professor, ウイルス研究所, 教授 (40072946)

Co-Investigator(Kenkyū-buntansha) IDO Eiji  Kyoto University, Institute for Vitus Research, Assistant professor, ウイルス研究所, 助手 (70183176)
榎瀬 良美  京都大学, ウイルス研究所, 日本学術振興会特別研究員(PD)
Project Period (FY) 2002 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥64,000,000 (Direct Cost: ¥64,000,000)
Fiscal Year 2005: ¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2004: ¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2003: ¥16,000,000 (Direct Cost: ¥16,000,000)
Fiscal Year 2002: ¥18,000,000 (Direct Cost: ¥18,000,000)
KeywordsAIDS / DNA vaccine / AIDS vaccine / SIV / SHIV / monkev / mucosal infection / mucosal immunity / HIV / ウイルス体内分布 / 分化障害 / SIV / γδ細胞 / NK活性 / 経粘膜感染 / アカゲザル / 樹状細胞 / マクロファージ
Research Abstract

In order to clarify the mechanisms of mucosal infection and mucosal immunity of HIV-1, we have tried to establish the monkey experimental model system of mucosal infection using SIV and SHIV and to see the virus spread and immune response for protection. Results obtained are followed.
1. Immunities and protective effect of nonpathogenic SHIV against mucosal infection (2001).
Involvement of 7 5 T and NK as well as acquired immunities was shown in the protection against intrarectal attack infection of pathogenic SHIV in the monkeys immunized with nef-deleted nonpathogenic SHIV.
2. Virus population through SIV intravaginal infection (2002).
Virus population was restricted when it passed through mucosa and it had no relation to viral cell tropisms.
3. Virus spread and immune responses at the early phase of intrarectal infection of acute pathogenic SHIV (2003).
Immediately after intrarectal infection, the virus spread in a whole body, not replicating at the mucosal sites. The CD4 cell decrease was prominent especially in thymus in which impairment of T cell maturation was ex vivo demonstrated.
4. Virus spread and immune responses at the early phase of intrarectal infection of low pathogenic SHIV (2004).
Virus replicated and induced CD4 cell depletion at the rectal sites, and gradually spread to a whole body in which CD4 depletion was slight.
5. Vaccination with SHIV DNA which produces noninfectious virions protected mucosal infection (2005).
SHIV mutant DNA lacking packaging ability induced protective effect against intrarectal attack infection of acute pathogenic SHIV.
Close association of virus spread and immure response with prognosis had been suggested in HIV1 infection. This study experimentally proved it by using monkeys. The obtains results are important and useful for develonment of effeetive vaepine develonment

Report

(5 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (37 results)

All 2006 2005 2004 2003 2002 2001 Other

All Journal Article (24 results) Publications (13 results)

  • [Journal Article] DNA vaccination of macaques by a full-genome SHIV plasmid that has an IL-2 gene and produces non-infection virus particles2006

    • Author(s)
      Horiuchi, R., Akahata, W., Kuwata, T., Enose, Y., Ido, E., Suzuki, H., Miyake, A., Saito, N., Ibuki, K., Goto, T., Miura, T., Hayami, M.
    • Journal Title

      Vaccine 24,17

      Pages: 3677-3685

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] DNA vaccination of macaques by a full-genome SHIV plasmid that has an IL-2 gene and produces non-infectious virus particles2006

    • Author(s)
      Horiuchi, R., Akahata, W., Kuwata, T., Enose, Y., Ido, E., Suzuki, H., Miyake, A., Saito, N, Ibuki, K., Goto, T., Miura, T., Hayami, M.
    • Journal Title

      Vaccine 24(17)

      Pages: 3677-3685

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Construction and int vitro characterizition of a chimeric simian and human immunodeficiency virus with the RANTES gene2006

    • Author(s)
      Shimizu, Y., Okoba, M., Yamazaki, N., Goto, Y., Miura, T., Hayami, M., Hoshino, H., Haga, T.
    • Journal Title

      Microbe & Infect 8

      Pages: 105-113

    • Related Report
      2005 Annual Research Report
  • [Journal Article] DNA vaccination of macaques by a full-genome SHIV plasmid that has an IL-2 gene and Produces non-infectious virus particles2006

    • Author(s)
      Horiuchi, R., Akahata, W., Kuwata, T., Enose, Y., Ido, E., Suzuki, H., Miyake, A., Saito, N., Ibuki, K., Goto, T., Miura, T., Hayami, M.
    • Journal Title

      Vaccine 24;17

      Pages: 3677-3685

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Early virological events in various tissues of newborn monkeys after intrarectal infection with pathogenic simian human immunodeficiency virus2005

    • Author(s)
      Miyake, A., Ibuki, K., Suzuki, H., Horiuchi, R., Saito, N., Motohara, M., Hayami, M., Miura, T.
    • Journal Title

      J.Med.Primat 34

      Pages: 294-302

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Induction of immune response, in macaque monkeys infected with simian-human immunodeficiency virus having the TNF-alpha gene at an early stage of infection2005

    • Author(s)
      Shimizu, Y., Miyazaki, Y., Ibuki, K., Suzuki, H., Kaneyasu, K., Goto, Y., Hayami, M., Miura, T., Haga, T.
    • Journal Title

      Virology 20;343(2)

      Pages: 151-161

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Intrathymic Effect of Acute Pathogenic SHIV Infection on T-Lineage Cells in Newborn Macaques2005

    • Author(s)
      Suzuki, H., Motohara, M., Miyake, A., Ibuki, K., Fukazawa, Y., Inaba, K., Masuda, K., Minato, N., Kawamoto, H., Hayami, M., Miura, T.
    • Journal Title

      Microbiol.Immunol 49(7)

      Pages: 667-679

    • NAID

      10016567960

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Comparison of susceptibility to SIVmac239 infection between CD4+ and CD4+8+ T cells2005

    • Author(s)
      Takahashi, M., Ido, E., Uesaka, H., Fukushima, T., Ibuki, K., Miura, T., Hayami, M., Takahashi, H.
    • Journal Title

      Archives of Virology 150

      Pages: 1517-1528

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The quantity and diversity of infection viruses in various tissues of SHIV-infected monkeys at the early and AIDS stages2004

    • Author(s)
      Miyake, A., Enose, Y., Ohkura, S., Suzuki, H., Kuwata, T., Shimada, T., Kato, S., Narayan, O., Hayami, M.
    • Journal Title

      Arch. Virol. 149

      Pages: 943-955

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The quantity and diversity of infectious viruses in various tissues of SHIV-infected monkeys at the early and AIDS stages2004

    • Author(s)
      Miyake, A., Enose, Y., Ohkura, S., Suzuki, H., Kuwata, T., Shimada, T., Kato, S., Narayan, O., Hayami,M.
    • Journal Title

      Arch. Virol. 149

      Pages: 943-955

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Induction of HIV-specific antibody response an protection against vaginal SHIV transmission by intranasal immunization with inactivated SHIV-capturing nanospheres in Macaques.2004

    • Author(s)
      Miyake, A., Hayami, M., et al.
    • Journal Title

      J.Med.Virol 73

      Pages: 368-377

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Augmentation of antigen-specific cytokine responses in the early phase of vaccination with a live-attenuated simian/human immunodeficiency chimeric virus expressing IFN-γ.2004

    • Author(s)
      Iida, T., Hayami, M., et al.
    • Journal Title

      Arch.Virol. 149

      Pages: 743-757

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Protective effects of nef-deleted SHIV or that having IFN-γ against disease induced with a pathogenic virus early after vaccination.2004

    • Author(s)
      Enose, Y., Hayami, M., et al.
    • Journal Title

      Arch.Virol. 149

      Pages: 1705-1720

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Linkage of amino acid variation an evolution of human Immunodefisiency virus type 1 gp120 envelope glycoprotein(subtype B)with usage of the second receptor.2004

    • Author(s)
      Yamaguchi-Kabata, Y., Hayami, M et al.
    • Journal Title

      J.Mol Evol. 58

      Pages: 333-340

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The quantity and diversity of infectious viruses in various tissues of SHIV-infected monkeys at the early and AIDS stages.2004

    • Author(s)
      Miyake, A., Hayami, M., et al.
    • Journal Title

      Arch.Virol 149

      Pages: 943-955

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Phylogenetic analysis of derived from mandrill and drill.2004

    • Author(s)
      Takemura, T., Hayami, M., et al.
    • Journal Title

      Frontiers in Bioscience. 9

      Pages: 513-520

    • Related Report
      2004 Annual Research Report
  • [Journal Article] HIVの病原性とエイズ弱毒性生ワクチン開発・・・サルを用いたモデル2004

    • Author(s)
      速水正憲, 堀内励生
    • Journal Title

      ウイルス 54

      Pages: 75-82

    • Related Report
      2004 Annual Research Report
  • [Journal Article] DNA vaccination of macaques by a full genome SHIV-1 plasmid chimera that produces non-infectious virus particles2003

    • Author(s)
      Akahata, W., Ido, E., Akiyama, H., Uesaka, H., Enose, Y., Horiuchi, R., Kuwata, T., Goto, T., Takahashi, H., Hayami, M.
    • Journal Title

      J. Gen. Virol. 84

      Pages: 2237-2244

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Construction and in vivo infection of anew simian/human immunodeficiency virus chimera containing the reverse transcriptasegene and the 3' half of the genomic region of human immunodeficiency virus type 12003

    • Author(s)
      Akiyama, H., Ido, E., Akahata, W., Kuwata, T., Miura, T., Hayami, M.
    • Journal Title

      J. Gen. Virol. 84

      Pages: 1663-1669

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Construction and in vivo infection of a new simian/human immunodeficiency virus chimera containing the reverse transcriptase gene and the 3' half of the genomic region of human immunodeficiency virus type 12003

    • Author(s)
      Akiyama, H., Ido, E., Akahata, W, Kuwata, T., Miura, T., Hayami, M.
    • Journal Title

      J. Gen. Virol. 84

      Pages: 1663-1669

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Protection by intranasal immunization of anef-deleted, nonpathogenic SHIV against intravaginal challenge with a heterologous pathogenic SHIV2002

    • Author(s)
      Enose, Y., Ui, M., Miyake, A., Suzuki, H., Uesaka, H., Kuwata, T., Kunisawa, J., Kiyono, H., Takahashi, H., Miura, T., Hayami, M.
    • Journal Title

      Virology. 298

      Pages: 306-316

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Protection by intranasal immunization of a nef-deleted, nonpathogenic SHIV against intravaginal challenge with a heterologous pathogenic SHIV2002

    • Author(s)
      Enose, Y., Ui, M., Miyake, A., Suzuki, H., Uesaka, H., Kuwata, T., Kunisawa, J., Kiyono, H., Takahashi, H., Miura, T., Hayami,M.
    • Journal Title

      Virology. 298

      Pages: 306-316

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Characterrization of less pathogenic infectious molecular clones derived from acute-pathogrnic ShIV-89.6P stock virus2001

    • Author(s)
      Kozyrev, IL., Ibuki, K., Shimada, T., Kuwata, T., Takemura, T., Hayami, M., Miura, T.
    • Journal Title

      Virology. 282

      Pages: 6-13

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Characterization of less pathogenic infectious molecular clones derived from acute-pathogenic SHIV-89.6P stock virus2001

    • Author(s)
      Kozyrev, 1 L., Ibuki, K., Shimada, T., Kuwata, T., Takemura, T., Hayami, M., Miura, T.
    • Journal Title

      Virology 282

      Pages: 6-13

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] Shimda, T, Hayami, M, et al.: "Comparetive histopathological studies in the early stage of a cute pathogenic and nonpathogenic SHIV-infected lymphoid organs"Virology. 306. 334-336 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Haga T, Hayami M, et al.: "Characterization of vpr Vector Constructed from Chimeric Simian and Human Immunodeficiency Virus"J.Vet.Med.Scie. 65. 633-636 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Enose Y, Hayami M, et al.: "Infection of a chimeric simian and human immunodeficiency virus with CCR5-specific HIV-I envelope to rhesus macaques"J.Vet.Med.Scie. 65. 283-285 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Akahata W, Hayami M et al.: "DNA vaccination of macaques by a full-genome SHIV-I plasmid that produces non-infectious virus particles"J.Gen.Virol. 84. 2237-2244 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Akahata W, Hayami M et al.: "Mutational analysis of two zinc-finger motifs in the mucleocapsid protein of simian immunodeficiency virus mac239"J.Gen.Virol. 84. 1641-1648 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Akiyam H, Hayami M et al.: "Construction and in vivo infection of a new simian/human immunodeficiency virus chimera containing the reverse transcriptase gene and the 3' half of the genomic region of human immunodeficiency virus type"J.Gen.Virol. 84. 1663-1669 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Iida T, Hayami M et al.: "Augmentation of antigen-specific cytokine responses in the early phase of vaccination with a live-attenuated simian/human immunodeficiency chimeric virus expressing IFN-gamma."Arch.Virol. (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ariko M, Hayami M et al.: "Induction of HIV-specific antibody response and protection against vaginal SHIV transmission by intranasal immunization with inactivated SHIV-capturing nanospheres in macaques."J.Med.Virol. in press. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kozyrev, I.: "Co-expression of interleukin-5 influences replication of simian/human immunodeficiency virus in vivo"J. Gen. Virol.. 83. 1183-1188 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Enose, Y.: "Protection by intranasal immunization of a nef-deleted, nonpathogenic SHIV against intravaginal challenge with a heterologous pathogenic SHIV"Virology. 298. 306-316 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kwofie, T.: "Characterization of simian and human immunodeficiency chimeric viruses re-isolated from vaccinated macaque monkeys after challenge infection"Arch. Virol.. 147. 1091-1104 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyazaki, Y.: "Analysis of a primary isolate-like virus from simian and human immunodeficiency virus-infected macaque having broad neutralizing activity"AIDS Res. Hum. Retroviruses. 18. 469-475 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kuwata, T.: "Infection of macaques with chimeric simian and human immunodeficiency viruses containing Env from subtype F"Arch, Virol.. 147. 1121-1132 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2018-03-28  

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