Molecular Mechanism of Virus-Induced Cell damage and its regulation

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。我们发现了一个有趣的细胞融合诱导系统，在这个系统中，副粘病毒的融合蛋白(F)单独可以诱导多核巨细胞。我们还发现了SV5的两种F蛋白，即一种不含HN蛋白的SV 5的F蛋白具有诱导细胞融合的能力，另一种F蛋白可以在HN蛋白的辅助下诱导细胞融合。这些F蛋白之间有三个氨基酸差异，我们鉴定了F蛋白单独诱导细胞融合的氨基酸。我们先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(FRPS)-1和-2调控。我们分离了8株针对FRP-1分子的单抗，并阐明了它们的功能。抗FRP-1抗体可分为三类，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抗体既有促进细胞融合的作用，也有抑制细胞融合的作用，可以刺激细胞内信号传导。然而，我们找不到这些解毒剂诱导的信号之间的差异。我们还分离了19株针对小鼠FRP-1的单抗。小鼠FRP-1为同种异体抗原，与Ly-10同种异体抗原相同。

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.