| Project/Area Number |
02404026
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
KATUNUMA Nobuhiko Institute for Enzyme Research The University of Tokushima, Professor, 酵素科学研究センター, 教授 (50035375)
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| Co-Investigator(Kenkyū-buntansha) |
TOWATARI Takae Institute for Enzyme Research The University of Tokushima, Assistant, 酵素科学研究センター, 助手 (60108876)
KIDO Hiroshi Institute for Enzyme Research The University of Tokushima, Associate Professor, 酵素科学研究センター, 助教授 (50144978)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥32,400,000 (Direct Cost: ¥32,400,000)
Fiscal Year 1991: ¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1990: ¥26,300,000 (Direct Cost: ¥26,300,000)
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| Keywords | Retrovirus / AIDS / CD4 / Trypstatin / Tryptase / V3 domain / エイズウイルス / gp120 / 感染機序 |
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| Research Abstract |
Infection by human immunodeficiency virus (HIV) is due to virus-cell fusion mediated by interaction of the envelope glycoprotein (gp120) of HIV with the CD4 molecule present on the surface of T4^+ lymphocytes. However, the CD4 molecule may not be the only component of HIV receptor because mouse cells expressing the human CD4 molecule are not infected by HIV. We recently found a novel membrane-bound serine protease, named tryptase TL2, other than CD4 receptor in human T4^+ lymphocytes which specifically binds the V3 domain of HIV gp120. The enzyme has a molecular mass of 198KDa and is composed of two subunits of 32KDa and four subunits of 28KDa. Cell surface radioiodination indicated that the subunit of 32KDa is exposed on the surface of T lymphocyte and binds to the V3 domain of HIV gp120. Scatchard analysis revealed a single class of gp120 binding site on tryptase TL2 with an apparent dissociation constant of 3.8 x 10^<-8>M for tryptase TL2. The V3 domain has been reported to be the principal neutralizing determinant of HIV and also to be a determinant for cellular tropism of HIV infection. Antibody against the V3 domain and that against tryptase TL2, kunitz-type inhibitors of tryptase TL2 and synthetic V3 domain peptides of various. HIV strains effectively inhibited the binding of gpl2O to tryptase TL2. These antibodies, the inhibitors and the peptides also inhibited syncytia formation induced by HIV. These results suggest that Tryptase TL2 is important in target site recognition and binding of HIV in the initial process of HIV infection. The studies on the role of tryptase TL2 in the process of membrane fusion in co-operation with CD4 receptor is now in progress
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