Difference in molecular mechanism between envelope-cell fusion and cell-cell fusion.
| Project/Area Number |
15590414
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Mie University |
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Principal Investigator |
TSURUDOME Masato Mie University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (50159042)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | simian virus 5 / human parainfuenza virus type 2 / membrane fusion / HN protein / F protein / monoclonal antibody / neuraminidase / reverse genetics / パラミクソウイルス / パラインフルエンザ2型ウイルス / Escape mutant / 細胞膜-細胞膜融合 / 構造変化 / 多核巨細胞 / 分子モデリング / 負電荷間相互作用 / モノクロナール抗体 |
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| Research Abstract |
1.By replacing Leu-22 of the F protein of simian virus 5 (WR strain) with Pro, a mutant F protein, L22P, was obtained which induced the HN-independent cell-cell fusion. Mutational analysis of L22P has suggested that either the hydrophobic interaction between the F2 N-terminus and fusion peptide or the electrostatic interaction between the HR1 domain and a region downstream of the Cys-rich domain affects the fusing activity of L22P.
2.Se-L22P is a mutant F protein, in which the cleavage site of L22P is replaced with that of the Sendai virus F protein. As the result, Se-L22P can be cleaved and can induce cell-cell fusion only when treated with trypsin. We found that Se-L22P located in the nonraft domains, but not in the raft domains, of the plasma membrane undergoes a conformational change upon treatment with trypsin and that cell-cell fusion is induced after this conformational change.
3.By propagating human parainfluenza virus type 2 (PIV2:Toshiba strain) in the presence of an anti-HN monoclonal antibody (M1-1A), an escape mutant, F13, was selected which exhibited very low pathogenicity (or cell-cell fusion). Analysis employing a set of mutant viruses that were produced by reverse genetics, it has been shown that mutations at positions 83 and 186 of the F13 HN protein are both required for the low cytopathogenicity, whereas these mutations do not affect virus-cell fusion. These results suggest that there is difference in molecular mechanism between cell-cell fusion and virus-cell fusion and that an unknown cellular factor in the infected cell is involved. In contrast to PIV3, no correlation was observed between the neuraminidase activity and the cytopathogenicity of PIV2, suggesting that the difference in virulence between PIV2 and PIV3 may reflect the difference in neuraminidase function.
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Report
(3 results)
Research Products
(23 results)
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[Journal Article] Early stage of establishment process of Sendai virus persistent infection : an unstable dynamic phase and then selection of viruses which are tightly cell-associated, temperature-sensitive and capable of establishing persistent infection.2004
Author(s)
Ito, M., Takeuchi, T., Nishio, M., Kawano, M., Komada, H., Tsurudome.M., Ito, Y.
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Journal Title
Journal of Virology 78(21)
Pages: 11939-11951
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Recombinant Sendai viruses with L1618V mutation in their L polymerase establish persistent infection, but not temperature sensitivity.2004
Author(s)
Nishio, M., Nagata, A., Tsurudome.M., Ito, M., Kawano, M., Komada, H., Ito, Y.
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Journal Title
Virology 329(2)
Pages: 289-231
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] The functional interaction between CD98 and CD147 in regulation of virus-induced cell fusion and osteoclast formation.2004
Author(s)
Mori, K., Nishimura, M., Tsurudome.M., Ito, M., Nishio, M., Kawano, M., Kozuka, Y., Yamashita, Y., Komada, H., Uchida, A., Ito, Y.
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Journal Title
Medical Microbiology and Immunology (Berl) 193(4)
Pages: 155-162
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The targeted disruption of the CD98 gene results in embryonic lethality.2003
Author(s)
Tsumura, H., Suzuki, N., Saito, H., Kawano, M., Otake, S., Kozuka, Y., Komada, H., Tsurudome, M., Ito, Y.
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Journal Title
Biochemical and Biophysical Research Commununications 308(4)
Pages: 847-851
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Characterization of Sendai virus persistently infected L929 cells and Sendai virus pi strain : recombinant Sendai viruses having Mpi protein shows lower cytotoxicity and are incapable of establishing persistent infection.2003
Author(s)
Nishio, M., Tsurudome, M., Ito, M., Kawano, M., Komada, H., Ito, Y.
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Journal Title
Virology 314(1)
Pages: 110-124
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Identification of amino acids essential for the human parainfluenza type 2 virus V protein to lower the intracellular levels of the STAT2.2003
Author(s)
Kozuka, Y., Yamashita, Y., Kawano, M., Tsurudome, M..Ito, M., Nishio, M., Komada, H., Ito, Y.
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Journal Title
Virology 317(2)
Pages: 208-219
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Identification of paramyxovirus V protein residues essential for STAT protein degradation and promotion of virus replication.
Author(s)
Nishio, M., Tsurudome, M., Ito.M.,.Garcin, D., Kolakofsky, D., Ito, Y.
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Journal Title
Journal of Virology (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cytological properties of stromal cells derived from giant cell tumor of bone (GCTSC) which can induce osteoclast formation of human blood monocytes without cell to cell contact.
Author(s)
Nishimura, M., Yuasa, K., Mori, K., Miyamoto, N., Ito, M., Tsurudome, M., Nishio, M., Kawano, M., Komada, H., Ito, Y.
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Journal Title
Journal of Orthopaedic Research (in press)
Description
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Related Report
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