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Developement of cell adhesion factor like anti-viral agents

Research Project

Project/Area Number 09557027
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Virology
Research InstitutionMie University

Principal Investigator

ITO Yasuhiko  Mie University, Faculty of Medicine, Professor, 医学部, 教授 (00022872)

Co-Investigator(Kenkyū-buntansha) YOSHINAKA Yoshiyuki  Otsuka Institute, Microbiology, Chief, 微生物研究所, 部長 (30024657)
KOMADA Hiroshi  Suzuka University, Medical Science and Technology, Associate Professor, 一般教養部, 助教授 (10144247)
NISHIO Machiko  Mie University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (70156040)
KAWANO Mitsuo  Mie University, Faculty of Medicine, Lecture, 医学部, 講師 (00234097)
TSURUDOME Masato  Mie University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (50159042)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1998: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1997: ¥4,600,000 (Direct Cost: ¥4,600,000)
KeywordsHIV / PARAMYXOVIRUS / FRP-1 / CD98 / PROTEIN KINASE / インテグリン
Research Abstract

We analyzed the mechanisms of virus (paramyxoviruses and HIV)-induced cell damage. We isolated 9 monoclonal antibodies directed against FRP-l molecules and clarified their abilities. Anti-FRP- 1 antibodies can be classified into three groups, namely, cell fusion enhancing antibodies, cell fusion suppressing antibodies and antibody showing no activity. Anti-FRP- 1 antibody, both cell fusion enhancing and suppressing antibodies, can stimulate intracellular signaling. However, we could not find the difference between these antidodies-induced signaling. We also isolate 19 monoclonal antibodies directed against murine FRP-1. Murine FRP-1 was found to be alloantigens and to be identical to Ly10 alloantigens. We showed that there were two different FRP-1-mediated signal pathways, that is, positive and negative signaling. Furthermore, we cloned FRP-1/CD90 light chain cDNA and carried out chromosomal mapping of FRP-1/CD90 light chain. We found an interesting cell fusion induction system, in which fusion (F) protein of paramyxovirus alone can induce multinucleated giant cells. We also found that there were two kinds of F protein of SV 5, that is, one F protein of SV 5 has an ability for induction cell fusion without HN protein and other F protein can induce cell fusion by an assistance of HN protein. There are three amino acid differences between these F proteins, and we identified amino acid responsible for inducibility of cell fusion by F protein alone.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (42 results)

All Other

All Publications (42 results)

  • [Publications] Kousuke Okamoto: "An Anti-Fusion Regulatory Protein-1 (FRP-1) Monoclonal Antibody Suppresses Human Parainfluenza Type 2 Virus-Induced Cell Fusion" J.Gen.Virology. 78. 83-89 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kousuke Okamoto: "Paramyxovirus-induced syncytium cell formation is suppressed by a dominant negative fusion regulatory protein-1 (FRP-1)/CD98 mutated construct." J.Gen.Virology. 78. 775-783 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shigeru Suga: "Human Immunodeficiency Virus Type-1 Envelope Glycoprotein gp120 Induce Expression of Fusion Regulatory Protein (FRP)-1/CD98 on CD4+ T Cells" Medical Microbiology and Immunology. 185. 237-243 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Machiko Nishio: "Mapping of Epitopes Recognized by Monoclonal Antibodies Directed Against the P hosphoprotein of Human Parainfluenza Virus Type 2 and the Location of Its Multimerization" J.Gen.Virology. 78. 1303-1308 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nobutada Tabata: "Involvement of Various Protein Kinases in Anti-FRP-1/CD98/4F2 mAb-Induced Cell Fusion Mediated by HIV gp160" Medical Microbiology and Immunology. 186. 115-123 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kousuke Okamoto: "Enhancement of human parainfluenza virus-induced cell fusion by pradimicin, a low molecular weight mannose-binding antibiotic" Medical Microbiology and Immunology. 186. 101-108 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Morihiro Ito: "Role of a single amino acid at the amino terminus of the simian virus 5 F2 subunit in syncytium formation" J.Virology. 71. 9855-9858 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masato Tsurudome: "Identification of regions on the fusion protein of human parainfluenza type 2 virus which are required for haemagglutinin-neuraminidase proteins to promote cell fusion" J.Gen.Virology. 79. 279-289 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shigeomi Higuchi: "Induction of Human Osteoclast-like Cells by Treatment of Blood Monocytes with Anti-Fusion Regulatory Protein-1/CD98 Monoclonal Antibodies" J.Bone and Mineral Research. 13. 44-49 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Murphy: "A functional antigenomic promoter for the paramyxovirus simian virus 5 requires proper spacing between an essential internal segment and the 3' terminus" J.Virology. 72. 10-19 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hideki Tsumura: "Mouse alloantigen, Ly10, Is Identical to Murine Fusion Regulatory Protein-1(mFRP-1)/4F2/CD98" Cellular Immunology. 184. 153-160 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hideki Tsumura: "Detection of endogenous retrovirus antigens in NOD mouse pancreatic beta-cells" Lab.Anim.32. 86-94 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hideki Tsumura: "Isolation and Characterization of Monoclonal Antibodies Directed Against Murine FRP-1" Immunology and Cell Biology. 77. 19-27 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masato Tsurudome: "Primary Structure of the Light Chain of Fusion Regulatory Protein-1/CD98/4F2 Predicts a Protein with Multiple Transmembrane Domains That Is Almost Identical to the Amino Acid Transporter E16" J.Immunology. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masanori Tajimao: "Suppression of FRP-1/CD98-Mediated Multinucleated Giant Cell and Osteoclast Formation by of Anti-FRP-1/CD98 mAb, HBJ 127, That Inhibits c-src Expression One" Cellular Immunology. 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.Okamoto, M.Tsurudome, S.Ohgimoto, M.Kawano, M.Nishio, H.Komada, M.Ito, Y.Sakakura, and Y.Ito: "An Anti-Fusion Regulatory Protein-1 (FRP-1) Monoclonal Antibody Suppresses Human Parainfluenza Type2 Virus-Induced Cell Fusion" J.Gen.Virology. 78. 83-89 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Okamoto, S.Ohgimoto, M.Nishio, M.Tsurudome, M.Kawano, H.Komada, M.Ito, Y.Sakakura, and Y.Ito: "Paramyxovirus-induced syncytium cell formation is suppressed by a dominant negative fusion regulatory protein-1 (FRP-1)/CD98 mutated construct : an important role of FRP-1 in virus-induced cell fusion" J.Gen.Virology. 78. 775-783 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Suga, M.Tsurudome, M.Ito, S.Ohgimoto, N.Tabata, M.Nishio, M.Kawano, H.Komada, M.Ito, M.Sakuraiand Y.Ito: "Human Immunodeficiency Virus Type-1 Envelope Glycoprotein gp120 Induce Expression of Fusion Regulatory Protein (FRP)-1/CD98 on CD4+T Cells : A Possible Regulatory Mechanism of HIV-Induced Syncytium Formation" Medical Microbiology and Immunology. 185. 237-243 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Nishio, M.Tsurudome, M.Ito, N.Watanabe, M.Kawano, H.Komada, and Y.Ito: "Mapping of Epitopes Recognized by Monoclonal Antibodies Directed Against the Phosphoprotein of Human Parainfluenza Virus Type2 and the Location of Its Multimerization" J.Gen.Virology. 78. 1303-1308 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] N.Tabata, M.Ido, S.Suga, S.Ohgimoto, M.Tsurudome, M.Kawano, M.Nishio, N and Y.Ito: "Involvement of Various Protein Kinases in Anti-FRP-1/CD98/4F2 mAb-Induced Cell Fusion Mediated by HIV gp160 : Protein Tyrosine Kinase Activation Provides an Early and Obligatory Signal in FRP-1-Induced Cell Fusion" Medical Microbiology and Immunology. 186. 115-123 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Okamoto, T.Oki, Y.Igarashi, M.Tsurudome, M.Nishio, M.Kawano, H.Komada, M.Ito, Y.Sakakura, and Y.Ito: "Enhancement of human parainfluenza virus-induced cell fusion by pradimicin, a low molecular weight mannose-binding antibiotic" Medical Microbiology and Immunology. 186. 101-108 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Ito, M.Nishio, M.Kawano, S.Kusagawa, H.Komada, Y.Ito, and M.Tsurudome: "Role of a single amino acid at the amino terminus of the simian virus 5 F2 subunit in syncytium formation" J.Virology. 71. 9855-9858 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Tsurudome, M.Ito, M.Nishio, M.Kawano, S.Kusagawa, H.Komada, and Y.Ito: "Identification of regions on the fusion protein of human parainfluenza type 2 virus which are required for haemagglutinin-neuraminidase proteins to promote cell fusion" J.Gen.Virology. 79. 279-289 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Higuchi, N.Tabata, M.i Tajima, M.Ito, M.Tsurudome, A.Sudo, A.Uchida and Y.Ito: "Induction of Human Osteoclast-like Cells by Treatment of Blood Monocytes with Anti-Fusion Regulatory Protein-1/CD98 Monoclonal Antibodies" J.Bone and Mineral Research. 13. 44-49 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Murphy, Y.Ito, and G.D.Parks: "A functional antigenomic promoter for the paramyxovirus simian virus 5 requires proper spacing between an essential internal segment and the 3' terminus" J.Virology. 72. 10-19 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Tsumura, S.Kimura, M.Kawano, M.Tsurudome, K.Shimura and Y.Ito: "Mouse alloantigen, Ly10, Is Identical to Murine Fusion Regulatory Protein-1 (mFRP-1)/4F2/CD98 : Aberrant Expression of mFRP-1/Ly10 Allotypes in Cells Derived from CDF1 Mice due to the Gene Deletion." Cellular Immunology. 184. 153-160 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Tsumura, M.Miyazawa, S.Pgawa, JZ.Wang, Y.Ito and K.Shimura: "Detection of endogenous retrovirus antigens in NOD mouse pancreatic beta-cells" Lab.Anim.32. 86-94 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Tsumura, M.Kawano, M.Tajima, T.Kusaura, Y.Kozuka, S.Yoshimura, H.Komada, M.Tsurudome, M.Nishio, S.Kusagawa, K.shimura, and Y.Ito: "Isolation and Characterization of Monoclonal Antibodies Directed Against Murine FRP-1/CD98/4F2 Heavy Chain : Murine FRP-1 Is An Alloantigen and Amino Acid Change at 129 (P*R) is Related to the Alloantigenicity." 77. 19-27 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Tsurudome, M.Ito, S.Takebayashi, K.Okumura, M.Nishio, M.Kawano, S.Kusagawa, H.Komada, and Y.Ito: "Primary Structure of the Light Chain of Fusion Regulatory Protein-1/CD98/4F2 Predicts a Protein with Multiple Transmembrane Domains That Is Almost Identical to the Amino Acid Transporter E16" J.Immunology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Tajimao, S.Higuchi, Y.Higuchio, N.Miyamoto, A.Uchida, M.Ito, M.Nishio, H.Komada, M.Kawano, S.Kusagawao, M.Tsurudomeo and Y.Ito: "Suppression of FRP-1/CD98-Mediated Multinucleated Giant Cell and Osteoclast Formation by One of Anti-FRP-1/CD98 mAb, HBJ 127, That Inhibits c-src Expression" Cellular Immunology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shigeomi Higuchi: "Induction of human osteoclast-like cells by treatment of blood monocytes with anti-fusion regulatory protein-1/CD98 monoclonal antibodies." Journal of Bone and Mineral Research. Vol.13. 44-49 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masato Tsurudome: "Identification of regions on the fusion protein of human parainfluenza type 2 virus which are required for haemagglutinin-neuraminidase proteins to promote cell fusion." Journal of General Virology. Vol.79. 279-289 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hideki Tsumura: "Mouse alloantigen Ly10 is identical to murine fusion regulatory protein-1(mFRP-1)/4F2/CD98: Aberrant expression of mFRP-1/Ly10 allotypes in cells derived from CDF1 mice." Cellular Immunology. Vol.184. 153-160 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masato Tsurudome: "Primary structure of the light chain of FRP-1/CD98/4F2 predicts a protein with multiple transmembrane domains that is almost identical to the amino acid transporter E16." Journal of Immunology. Vol.162(in press). in the press (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Murphy,Y.: "A functional antigenomic promoter for the paramyxovirus simian virus 5 requires proper spacing between an essential internal segment and the 3' terminus" J.Virology. Vol.72. 10-19 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hideki Tsumura: "Isolation and Characterization of Monoclonal Antibodies Directed Against Murine FRP-1/CD98/4F2 Heavy Chain:" Immunology and Cell Biology.

    • Related Report
      1998 Annual Research Report
  • [Publications] Kousuke Okamoto: "An anti-fusion regulatory protein-1 monoclonal antibody suppresses human parainfluenza virus type 2-induced cell fusion." Journal of General Virology. Vol.78. 83-89 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kousuke Okamoto: "Paramyxovirus-induced syncytium cell formation is suppressed by a dominant negative fusion regulatory protein-1(FRP-1)/CD98 mutated construct." Journal of General Virology. Vol.78. 775-783 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kousuke Okamoto: "Enhancement of human parainfluenza virus-induced cell fusion by pradimicin,a low molecular weight mannose-binding antibiotic." Medical Microbiology and Immunology. Vol.186. 101-108 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shigeru Suga: "Human immunodeficiency virus type-1 envelope glycoprotein gp120 induces expression of fusion regulatory protein (FRP)-1/CD98 on CD4+T cells." Medical Microbiology and Immunology. Vol.186. 237-243 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Machiko Nishio: "Human parainfluenza virus type 2 phosphoprotein:Mapping of monoclonal antibody epitopes and location of the multimerization domain." Journal of General Virology. Vol.78. 1303-1308 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Morihiro Ito: "Role of a single amino acid at the amino terminus of the simian virus 5 F2 subunit in syncytium formation." Journal of Virology. Vol.71. 9855-9858 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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