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2004 Fiscal Year Final Research Report Summary

Analyses of host genes that confer immune resistance against human immunodeficiency virus type-1 infection in HIV-1-exposed but uninfected individuals in the overseas cohorts

Research Project

Project/Area Number 15406021
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section海外学術
Research Field Virology
Research InstitutionKinki University

Principal Investigator

MIYAZAWA Masaaki  Kinki University, School of Medicine, Professor, 医学部, 教授 (60167757)

Co-Investigator(Kenkyū-buntansha) TSUJI Sachiyo (KAWAHARA Sachiyo)  Kinki University, School of Medicine, Associate Professor, 医学部, 講師 (60297629)
KANARI Yasuyoshi  Kinki University, School of Medicine, Assistant Professor, 医学部, 助手 (60351590)
ABE Hiroyuki  Kinki University, School of Medicine, Assistant Professor, 医学部, 助手 (80309335)
Project Period (FY) 2003 – 2004
KeywordsHIV-1 / HIV-1-exposed but uninfected / chromosome 22 / mapping / DNA microarray / linkage disequilibrium / association / expression
Research Abstract

Despite multiple and repeated exprosures to HIV-1, some individuals possess no detectable HIV genome and show T-cell memory responses to the viral antigens. HIV-1-reactive mucosal IgA detected in such uninfected individuals suggests their possible immune resistance against HIV. We tested if the above HIV-1-exprosed but uninfected status was associated with genetic markers other than a homozygous deletion of the CCR5 gene.
Based on our mapping in chromosoma 15 of a gene controlling the production of neutralizing antibodies in a mouse retrovirus infection, we genotyped 42 HIV-1-exposed but uninfected Italians at polymorphic loci in the syntenic segment of human chromosome 22, and compared them with 49 HIV-1-infected and 47 uninfected healthy control individuals by a closed testing procedure. A significant association was found between chromosome 22q12-13 genotypes and a putative dominant locus conferring anti-HIV-1 immune responses in the exposed but uninfected individuals. Distributions of linkage disequilibrium across chromosome 22 also differed between the exposed but uninfected and two other phenotypic groups.
We next stimulated the peripheral blood mononuclear cells from HIV-1-exposed but uninfected and HIV-1-infected individuals with a mixture of HIV-1 gag and env antigens, and compared the expression of all the genes and open reading frames located in the above candidate region using a DNA microarray technique. Significant induction of several genes at 6 hours after the antigenic stimulation was observed only in the exposed but uninfected individuals. Further linkage of a single nucleotide polymorphism located in one candidate gene with the genotype of the D22S423 marker was observed only in the exposed but uninfected individuals. These data indicated the presence of a new genetic factor associated with the HIV-1-exposed but uninfected status.

  • Research Products

    (16 results)

All 2005 2004 2003

All Journal Article (15 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Genotypes at chromosome 22q12-13 are associated with HIV-1-exposed but uninfected status in Italians2005

    • Author(s)
      Kanari, Y., M.Clerici, H.Abe, H.Kawabata, D.Trabattoni, S.Lo Caputo, F.Mazzotta, H.Fujisawa, A.Niwa, C.Ishihara, Y.A.Takei, M.Miyazawa
    • Journal Title

      AIDS (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Genotypes at chromosome 22q12-13 are associated with HIV-1-exposed but uninfected status in Italians.2005

    • Author(s)
      Kanari, Y., M.Clerici, H.Abe, H.Kawabata, D.Trabattoni, S.Lo Caputo, F.Mazzotta, H.Fujisawa, A.Niwa, C.Ishihara, Y.A.Takei, M.Miyazawa
    • Journal Title

      AIDS (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Both T and non-T cells with proliferating potentials are effective in inducing suppression of allograft responses by alloantigen-specific intravenous presensitization combined with suboptimal doses of 15-deoxyspergualin2004

    • Author(s)
      Tahara H., N.Iwanami, N.Tabata, H.Matsumura, T.Matsuura, T.Kurita, M.Miyazawa
    • Journal Title

      Transplant.Immunol. 13

      Pages: 25-32

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Identification of a protective CD4^+ T-cell epitope in p15^<gag> of Friend murine leukemia virus and role of the MA protein targeting the plasma membrane in immunogenicity2004

    • Author(s)
      Sugahara, D., S.Tsuji-Kawahara, M.Miyazawa
    • Journal Title

      J.Virol. 78

      Pages: 6322-6334

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cytotoxic T lymphocyte-based control of simian immunodeficiency virus replication in a preclinical AIDS vaccine trial2004

    • Author(s)
      Matano, T., M.Kobayashi, H.Igarashi, A.Takeda, H.Nakamura, M.Kano, C.Sugimoto, K.Mori, A.Iida, T.Hirata, M.Hasegawa, T.Yuasa, M.Miyazawa, Y.Takahashi, M.Yasunami, A.Kimura, D.H.O'Connor, D.I.Watkins, Y.Nagai
    • Journal Title

      J.Exp.Med. 199

      Pages: 1709-1718

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Host genes that influence immune and non-immune resistance mechanisms against retrovrial infections2004

    • Author(s)
      Miyazawa, M
    • Journal Title

      Recent Res.Devel.Virol. 6

      Pages: 105-118

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Host genes that influence immune and non-immune resistance mechanisms against retrovrial infections.2004

    • Author(s)
      Miyazawa, M.
    • Journal Title

      Recent Res.Devel.Virol. 6

      Pages: 105-118

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Pathogenicity of autoantibodies reactive with the endogenous retroviral envelope glycoprotein gp70.2004

    • Author(s)
      Miyazawa, M., E.Kajiwara, N.Tabata, T.Ogawa, T.Yuasa, H.Matsumura
    • Journal Title

      From Animal Models to Human Genetics : Research on the Induction and Pathogenicity of Autoantibodies (K.Conrad, et al.editors). Pabst Science Publishers, Lengerich

      Pages: 85-96

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cytotoxic T lymphocyte-based control of simian immunodeficiency virus replication in a preclinical AIDS vaccine trial.2004

    • Author(s)
      Matano, T., M.Kobayashi, H.Igarashi, A.Takeda, H.Nakamura, M.Kano, C.Sugimoto, K.Mori, A.Iida, T.Hirata, M.Hasegawa, T.Yuasa, M.Miyazawa, Y.Takahashi, M.Yasunami, A.Kimura, D.H.O'Connor, D.I.Watkins, Y.Nagai
    • Journal Title

      J.Exp.Med. 199

      Pages: 1709-1718

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Identification of a protective CD4+ T-cell epitope in p15gag of Friend murine leukemia virus and role of the MA protein targeting to the plasma membrane in immunogenicity.2004

    • Author(s)
      Sugahara, D., S.Tsuji-Kawahara, M.Miyazawa
    • Journal Title

      J.Virol. 78

      Pages: 6322-6334

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Both T and non-T cells with proliferating potentials are effective in inducing suppression of allograft responses by alloantigen-specific intravenous presensitization combined with suboptimal doses of 15-deoxyspergualin.2004

    • Author(s)
      Tahara H., N.Iwanami, N.Tabata, H.Matsumura, T.Matsuura, T.Kurita, M.Miyazawa
    • Journal Title

      Transplant.Immunol. 13

      Pages: 25-32

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Gene structure and functional properties of mouse CRTH2, a prostaglandin D2 receptor2003

    • Author(s)
      Hirai, H., H.Abe, K.Tanaka, K.Takatsu, K.Sugamura, M.Nakamura, K.Nagata
    • Journal Title

      Biochem.Biophys.Res.Commun. 307

      Pages: 797-802

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] TCRδ gene rearrangements revealed by fine structure of the recombination junction in mice2003

    • Author(s)
      Kanari, Y., M.Muto, H.Yamagishi
    • Journal Title

      Microbiol.Immunol. 47

      Pages: 883-894

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Gene structure and functional properties of mouse CRTH2, a prostaglandin D2 receptor.2003

    • Author(s)
      Hirai, H., H.Abe, K.Tanaka, K.Takatsu, K.Sugamura, M.Nakamura, K.Nagata
    • Journal Title

      Biochem.Biophys.Res.Commun. 307

      Pages: 797-802

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] TCRδ gene rearrangements revealed by fine structure of the recombination junction in mice.2003

    • Author(s)
      Kanari, Y., M.Muto, H.Yamagishi
    • Journal Title

      Microbiol.Immunol. 47

      Pages: 883-894

    • Description
      「研究成果報告書概要(欧文)」より
  • [Patent(Industrial Property Rights)] Resistance Genes2004

    • Inventor(s)
      Miyazawa, M., M.Clerici, S.Irie
    • Industrial Property Rights Holder
      Immunoclin Ltd., Osaka Idustrial Promotion Organization, Toppan Printing Co.
    • Industrial Property Number
      UK Patent Application 0428301.6
    • Filing Date
      2004-12-23
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2006-07-11  

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