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Detection of bovine MHC genes associated with resistance or susceptibility to bovine leukemia virus-induced lymphoma

Research Project

Project/Area Number 13556055
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Applied veterinary science
Research InstitutionRIKEN

Principal Investigator

AIDA Yoko  RIKEN Retrovirus Research Unit,Unit leader, 分子ウイルス学研究ユニット, 研究ユニットリーダー (50182994)

Co-Investigator(Kenkyū-buntansha) TAJIMA Sigeru  RIKEN Retrovirus Research Unit,Special post doctoral fellow, 分子ウイルス学研究ユニット, 基礎科学特別研究員 (60311346)
森田 光夫  社団法人家畜改良事業団, 家畜改良技術研究所・遺伝検査部, 課長
森田 裕  チッソ株式会社, 新事業開発室, バイオセンサー部長
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2002: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2001: ¥8,900,000 (Direct Cost: ¥8,900,000)
KeywordsBovine MHC (BoLA)-DRB3 exon 2 / Bovine leukemia virus (BLV) / Polymorphism / Ovine MHC (OLA)-DRB1 / PCR-Sequence Based Typing / PCR-RFLP method / Disease susceptibility / BLV-induced lymphoma / BLV Env gp51抗原 / モノクローナル抗体 / PCR-Sequence Based Typing法 / ウシ主要組織適合抗原系統樹 / (BoLA)-DRB3 / 地方病性牛白血病(EBL) / PCR-Sequence-Based Typing(SBT)法 / 対立遺伝子頻度 / 同義置換・非同義置換
Research Abstract

Bovine leukemia virus (BLV) is known as an exogenous retrovirus associated with enzootic bovine leucosis (EBL), which is the most common neoplastic disease of cattle. We investigated the relationship between polymorphism of bovine MHC (BoLA) gene and resistance or susceptibility to BLV-induced lymphoma. The second exon of the BoLA class II DRB3 gene was sequenced for 81 BLV-infected animals with 3 independent stages such as an aleukemic healthy, persistent lymphocytosis and lymphoma. Sequence analysis revealed that alleles encoding Arg or Lys, Glu, Arg and Val at residues 71, 74, 77 and 78 of beta chain of DR might be related with resistance to tumor development.
Next, we developed a more precise method for sequence-based typing (SBT), which allows the identification of specific BoLA-DRB3 alleles in large numbers of animals. Using our SBT methods, we determined the nucleotide sequences of exon 2 of the BoLA-DRB3 alleles of a total of 471 individuals has belonged to four distinct breeds … More of catche, namely, Japanese Black, Japanese Shorthorn, Holstein and Jersey. We identified the 34 previously reported alleles and four novel alleles and the frequency of BoLA-DRB3 alleles in each breed.
We have reported previously that the alleles of the ovine leukocyte antigen (OLA)-DRB1 gene that encode the Arg-Lys (RK) motif and the Ser-Arg (SR) motif at positions b^<70/71> of the OLA-DRb1 domain are associated with resistance and susceptibility, respectively, to development of BLV-induced ovine lymphoma. Here, to investigate the different immune response in sheep that carried alleles associated with resistance and susceptible for 30 weeks after infection with BLV, we selected sheep that had the RK/RK or SR/SR genotype among the 52 sheep analyzed by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing of PCR product for the OLA-DRB1 exon 2 and infected them with BLV. The level of incorporation of [^3H]thymidine by peripheral blood mononuclear cells from the sheep with RK/RK genotype gave a strong response to BLV virion antigen and synthetic antigenic peptides that corresponded to T-helper epitope of the BLV envelope glycoprotein gp51. In contrast, the sheep with SR/SR genotype showed a strong response to BLV virion antigen and synthetic antigenic peptides that corresponded to T-cytotoxic and B-cell epitopes. In such cases, the animals with the RK/RK strongly expressed IFN-g, the animals with SR/SR genotype strongly expressed IL-2. To determine the proliferating cells, we tried a blocking assay with monoclonal antibodies such as anti-CD4, -CD8 and -DR molecule. We found that these proliferating cells were MHC-restricted CD4^+T-cells. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Takeshima S., et al.: "Indentification of new bovine BoLA-DRB3 alleles by sequence-based typing"Immunogenetics. 53. 74-81 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasuda J., et al.: "T cell apoptosis causes peripheral T cell depletionin mice transgenic for the HIV-1 vpr gene"Virology. 285. 181-192 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tana, et al.: "Growth inhibition of cancer cells by co-transfection of diphtheria toxin A-chain gene plasmid with bovine leukemia virus-Tax expression vector"Microbiol.Immunol.. 45. 447-455 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tajima S., et al.: "In vitro and In vivo analyses of infectious molecular clone of BLV encording tax with elevated transactivation activity"AIDS Research and Human Retroviruses. 17. S48 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aida Y., et al.: "Influence of host genetic differences on leukemogenesis induced bovine leukemia virus"AIDS Research and Human Retroviruses. 17. S12 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tajima S., et al.: "Mutant Tax protein from bovine leukemia virus with enhanced ability to activate the expression of c-fos"J.Virol.. 76. 2557-2562 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeshima S.m et al.: "Characterization of DRB3 alleles in the MHC of Japanese Shorthorn cattle by polymerase chain reaction-sequence-based typing"J.Dairy Sci.. 85. 1630-1632 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tajima S., et al.: "A mutant form of the Tax protein of bovine leukemia virus (BLV) with enhanced transactivation activity, increases the expression and propagation of BLV in vitro but not in vivo"J.Virol.. 77. 1893-1903 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Konnai S., et al.: "The influence of ovine MHC class II DRB1 alleles on immuno response in bovine leukemia virus infection"Microbiol.Immunol.. 47. 223-232 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tajima S., et al.: "Latency of viral expression in vivo is not related to CpG methylation in the U3 and part of the R region of the long terminal repeate of bovine leukemia virus"J.Virol.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Konnai S., et al.: "Seqense and diversity of 17 new Ovar-DRB1 alleles from three breeds of sheep"Eur.J.Immunogenet.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 間陽子: "農学領域におけるゲノムサイエンスの展開(Part2)"ウシゲノム解析と抗病性[1]""農業及び園芸. 76. 1187-1193 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 間陽子: "農学領域におけるゲノムサイエンスの展開(Part2)"ウシゲノム解析と抗病性[2]""農業及び園芸. 76. 1289-1294 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 間陽子: "獣医微生物学第2版(見上彪編)"文永堂出版(印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 間陽子: "医学書院医学大辞書(伊藤正男, 井村裕夫, 高久史麿総編集編)"医学書院(印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeshima S., Ikegami M., Morita M., Nakai Y. and Aida Y.: "Identification of new bovine BoLA-DRB3 alleles by sequence-based typing"Immunogenetics. 53. 74-81 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasuda J., Miyao T., Kamata M., Aida Y. and Iwakura Y.: "T cell apoptosis causes peripheral T cell depletion in mice transgenic for the HIV-1 vpr gene"Virology. 285. 181-192 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tana, Watarai S., Aida Y., Tajima S., Kaikidani H., Onuma M. and Kodama M.: "Growth inhibition of cancer cells by co-transfection of diphtheria toxin A-chain gene plasmid with bovine leukemia virus-Tax expression vector"Microbiol Immunol.. 45. 447-455 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tajima S., Takahashi M., Okada K. and Aida Y.: "In vitro and in vivo analyses of infectious molecular clone of BLV encoding tax with elevated transactivation activity"AIDS Resesch and Human Retroviruses. 17. S48 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aida Y.: "Influence of host genetic differences on leukemogenesis induced bovine leukemia virus"AIDS Resesch and Human Retroviruses. 17. S12 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tajima S. and Aida Y.: "Mutant Tax proteins from bovine leukemia virus with enhanced ability to activate the expression of c-fos"J. Virol. 76. 2557-2562 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeshima S., Nakai Y., Morita M. and Aida Y.: "Characterization of DRB3 alleles in the MHC of Japanese Shorthorn cattle by polymerase chain reaction-sequence-based typing"J. Dairy Sci.. 85. 1630-1632 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tajima S., Takahashi M., Takesihma S., Konnai S., Watarai S., Yin S. A., Tanaka Y., Onuma M., Okada K. and Aida Y.: "A mutant form of the Tax protein of bovine leukemia virus (BLV) with enhanced transactivation activiy, increases the expression and propagation of BLV in vitro but not in vivo"J. Virol. 77. 1894-1903 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Konnai S., Takeshima S., Tajima S., Yin S. A., Okada K., Onuma M. and Aida Y.: "The influence of ovine MHC class II DRB1 alleles on immuno response in bovine leukemia virus infection"Microbiol. Immunol.. 47. 223-232

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tajima S., Tsukamoto M. and Aida Y.: "Latency of viral expression in vivo is not related to CpG methylation in the U3 and part of the R region of the long teminal repeart of bovine leukemia virus"J.Virol. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Konnai S., Nagaoka Y., Takeshima S., Onuma M. and Aida Y.: "Sequence and diversity of 17 new Ovar-DRB1"Eur. J. Immunogenet.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeshima S., Nakai Y., Ohta M. and Aida Y.: "Tiping method of bovine major histocompatibility complex"Bulletin of the experimental Farm, Tohoku University. 17:. 19-28 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aida Y.: "Bovine genome analysis and disease resistance (1)"Agriculture and Horticulture. 76. 1187-1193 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aida Y.: "Bovine genome analysis and disease resistance (2)"Agriculture and Horticulture. 76. 1289-1294 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tajima S., et al.: "Mutant Tax protein from bovine leukemia virus with ability to activate the expression of c-fos"J.Virology. 76. 2557-2562 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tajima S., et al.: "A mutant form of the Tax ptrotein of bovine leukemia vitus (BLV) with enhanced transactivaton activiy, increases the expression and propagaion of BLV invitro but not in vivo"J.Virology. 77. 1894-1903 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takeshima, S., et al.: "Characterization of DRB3 alleles in the MHC of Japanese Shorthorn cattle by polymerase chain reaction-sequence-based typing"J.Dairy Science. 85. 1630-1632 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tajima S., et al.: "Latency of viral expression in vivo is not related to CpG methylation in the U3 and part of the R region of the long teminal repeart of bovine leukemia virus"J.Virology. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Konnai, S., et al.: "The influence of ovine MHC class II DRBI alleles on immuno response in bovine leukemia virus infection"Microbiol.Immunol.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takeshima S., Ikegami M., Morita M., Nakai Y., Aida Y: "Identification of new bovine BoLA-DRB3 alleles by sequence-based typing"Immunogenetics. 53. 74-81 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tana, Watarai S., Aida Y., Tajima S., Kaikidani H., Onuma M: "Growth inhibition of cancer cells by co-transfection of diphtheria toxin A-chain gene plasmid with bovine leukemia virus-Tax expression vector"Microbiol Immunol.. 45. 447-455 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tajima S., Aida Y.: "Mutant Tax proteins from bovine leukemia virus with ability to activate the cxpression of c-fos"J. Virology. 76. 2557-2562 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takeshima S., Nakai Y., Morita M., Aida Y: "Characterization of DRB3 alleles in the MHC of Japanese Shorthorn cattle by polymerase chain reaction-sequence-based typing"J. Dairy Science. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] 間陽子: "農学領域におけるゲノムサイエンスの展開(Part2)"ウシゲノム解析と抗病性[1]""農業および園芸. 76. 1187-1193 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 間陽子: "農学領域におけるゲノムサイエンスの展開(Part2)"ウシゲノム解析と抗病性[2]""農業および園芸. 76. 1289-1294 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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