Molecular Mechanism of Virus-Induced Cell damage and its regulation

病毒引起细胞损伤的分子机制及其调控

• 批准号: 08457096
• 负责人: ITO Yasuhiko
• 金额: $ 5.44万
• 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: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457096/
• 关键词: CELL FUSION; PARAMYXOVIRUS; FRP-1; HIV; Cell Fusion; CPE

We analyzed the mechanisms of cell fusion, multinucleated giant cell formation and virus entry using paramyxoviruses and HIV.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.We previously found that virus-induced cell fusion is regulated by some host cell factors, Fusion Regulatory Factors (FRPs)-1 and -2. We isolated 8 monoclonal antibodies directed against FRP-1 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 Ly 10 alloantigens.

我们利用副粘病毒和HIV分析了细胞融合、多核巨细胞形成和病毒侵入的机制，发现了一个有趣的细胞融合诱导系统，其中副粘病毒的融合蛋白（F）可以单独诱导多核巨细胞。SV 5的F蛋白有两种类型，一种F蛋白在没有HN蛋白的情况下具有诱导细胞融合的能力，另一种F蛋白在HN蛋白的辅助下具有诱导细胞融合的能力。这些F蛋白之间有三个氨基酸的差异，我们鉴定了单独F蛋白诱导细胞融合的氨基酸。我们以前发现，病毒诱导的细胞融合受一些宿主细胞因子，融合调节因子（FRP）-1和-2的调节。我们分离了8个抗FRP-1分子的单克隆抗体，并阐明了它们的能力。抗FRP-1抗体可分为三组，即细胞融合促进抗体、细胞融合抑制抗体和无活性抗体。抗FRP-1抗体，细胞融合增强和抑制抗体，可以刺激细胞内信号传导。然而，我们无法找到这些抗体诱导的信号之间的差异。我们还分离出19种针对鼠FRP-1的单克隆抗体。发现鼠FRP-1是同种异体抗原，并且与Ly 10同种异体抗原相同。

项目成果

Morihiro Ito: "Role of Single Amino Acid at the Amino Teminus of the Simian Virus 5F2 Subumit Syncytium Formation" Journal of Virology. VOL.71. 9855-9858 (1997)

Morihiro Ito：“单个氨基酸在猿猴病毒 5F2 亚群合胞体形成的氨基末端的作用”病毒学杂志。

Masato Turutomo: "Identification of Regions on the Fution Protein of Human Parainfluenza Type2 Virus which are Required for Haemagglutinin-Neuraminidase Proteins to Promote Cell Fution" Journal of General Virology. VOL.79. 279-289 (1998)

Masato Turutomo：“人副流感 2 型病毒融合蛋白区域的鉴定，这些区域是血凝素-神经氨酸酶蛋白促进细胞融合所必需的”普通病毒学杂志。

Kousuke Okamoto: "Enhancement of Human Parainfluenza Virus-induced Cell Fusion by Pradimicin Alow Molecular Weightmannose-Binding Antibiotic" Journal of General Virology. VOL.186. 101-108 (1997)

Kousuke Okamoto：“Pradimicin A 低分子量甘露糖结合抗生素增强人副流感病毒诱导的细胞融合”普通病毒学杂志。

N.Tabata, M.Ido, S.Suga, S.Ohgimoto, M.Tsurudome, M.Kawano, M.Nishio, N.Komada 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 Eady a

N.Tabata、M.Ido、S.Suga、S.Ohgimoto、M.Tsurudome、M.Kawano、M.Nishio、N.Komada 和 Y.Ito：“各种蛋白激酶参与抗 FRP-1/CD98

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 type2 virus which are required for haemagglutinin-neuraminidase proteins to promote cell fusion" J.General vir

M.Tsurudome、M.Ito、M.Nishio、M.Kawano、S.Kusakawa、H.Komada 和 Y.Ito：“鉴定人副流感 2 型病毒融合蛋白上血凝素-神经氨酸酶蛋白所需的区域