Molecular regulatory mechanism of virus-induced cell fusion

病毒诱导细胞融合的分子调控机制

• 批准号: 12470069
• 负责人: ITO Yasuhiko
• 金额: $ 7.74万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470069/
• 关键词: Paramyxoviridae; genus Rubulavirus; syncytium; CD147; ADAM9; monoclonal antibody; HIV; Osteoclast; パラミクソウイルス; FRP-1; CD98; 遺伝改変動物; LAT-1; ADAM; Cell fusion

Virus-induced cell fusion is regulated by the interaction between virus-factors and cellular factors. Fusion regulatory protein-1(FRP-1), which is identical with CD98, plays an important role on regulation of virus-induced cell fusion. FRP-1 is a multi-functional molecule, that is, FRP-1 can enhance and suppress virus-induced cell fusion. We constructed FRP-1 transgenic mice and knockout mice. FRP-1 knockout mice were found to be lethal, indicating FRP-1 that FRP-1 is essential and indispensable to ontogeny. In this study, we clarified that ADAM9 and CD147 molecules co-operated with FRP-1 in regulation of virus-induced cell fusion and monocytes fusion. ADAM9 is scarcely expressed on the blood monocytes, and expression of ADAM9 is induced by treatment of monocytes with anti-FRP-1 monoclonal antibody. An anti-ADAM9 antibody enhanced FRP-1-mediated cell aggregation, while it blocked FRP-1-mediated cell fusion. New protein synthesis is necessary for the expression of ADAM9 and genistein suppresses induction of ADAM9. One antibody to CD147 enhanced, white another one suppressed HIV-mediated cell fusion. Furthermore, we analyzed function of FRP-1 light chain, and discovered the N-light chains, which show high homology to FRP-1 light chain. We determined the cell and tissue distribution of the light chains and N-light chains. In this study, we established new method regulating virus induced cell fusion.

病毒诱导的细胞融合受病毒因子和细胞因子相互作用的调控。融合调节蛋白-1（FRP-1）与CD 98同源，在病毒诱导的细胞融合过程中起着重要的调节作用。FRP-1是一种多功能分子，即FRP-1可以增强和抑制病毒诱导的细胞融合。我们构建了FRP-1转基因小鼠和基因敲除小鼠。FRP-1敲除小鼠被发现是致命的，表明FRP-1，FRP-1是必不可少的和不可缺少的个体发育。在本研究中，我们阐明了ADAM 9和CD 147分子与FRP-1协同调节病毒诱导的细胞融合和单核细胞融合。ADAM 9在血液单核细胞上几乎不表达，并且通过用抗FRP-1单克隆抗体处理单核细胞来诱导ADAM 9的表达。抗-ADAM 9抗体增强FRP-1介导的细胞聚集，同时阻断FRP-1介导的细胞融合。新的蛋白质合成是必需的表达的ADAM 9和染料木黄酮抑制诱导的ADAM 9。一种CD 147抗体增强了HIV介导的细胞融合，另一种白色抗体抑制了HIV介导的细胞融合。进一步分析了FRP-1轻链的功能，发现了与FRP-1轻链具有高度同源性的N-轻链。我们确定了轻链和N-轻链的细胞和组织分布。本研究建立了调控病毒诱导细胞融合的新方法。

项目成果

Masanori Tajima: "Ability of osteoclast formation from peripheral monocytes using anti-fusion regulatory protein-1/CD98/4F2 monoclonal antibodies in patients with osteoporosis"Journal of Orthopedic Research. 18. 265-268 (2000)

Masanori Tajima：“在骨质疏松症患者中使用抗融合调节蛋白-1/CD98/4F2单克隆抗体从外周单核细胞形成破骨细胞的能力”骨科研究杂志。

Mitsuo Kawano: "Recovery of infectious human parainfluenza type 2 virus from cDNA clones and properties of the defective virus without V-Specific cysteine-rich domain"Virology. 284. 99-112 (2001)

Mitsuo Kawano：“从 cDNA 克隆中恢复传染性人类副流感 2 型病毒以及没有 V 特异性富含半胱氨酸结构域的缺陷病毒的特性”病毒学。

Masato Tsurudome: "Hemagglutinin-neuraminidase-independent fusion activity of simian virus 5 fusion (F) protein : difference in conformation between fusogenic and nonfusogenic F proteins on the cell surface"Journal of Virology. 75. 8999-9009 (2001)

Masato Tsurudome：“猿病毒5融合（F）蛋白的血凝素-神经氨酸酶独立融合活性：细胞表面融合和非融合F蛋白之间的构象差异”病毒学杂志。

Hiroshi Komada: "N-glycosylation contributes to the limited cross-reactivity between hemagglutinin neuraminidase proteins of human parainfluenza virus type 4A and 4B"Medical Microbiology and Immunology. Vol.189. 1-6 (2000)

Hiroshi Komada：“N-糖基化导致人副流感病毒 4A 型和 4B 型血凝素神经氨酸酶蛋白之间的有限交叉反应性”医学微生物学和免疫学。

Mitsuo Kawano: "Recovery of infectious humam parainfluenza type 2 virus from cDNA clones and properties of the defective virus without V-Specific cysteine-rich domain"Virology. Vol.284. 99-112 (2001)

Mitsuo Kawano：“从 cDNA 克隆中恢复传染性人类副流感 2 型病毒以及没有 V 特异性富含半胱氨酸结构域的缺陷病毒的特性”病毒学。