DETERMINANTS OF VIRAL MEMBRANE FUSION

这个项目的目的是调查两个新的发现 关于逆转录病毒和副粘病毒诱导的膜融合。 一个具体的目标是研究基因组中的序列 病毒糖蛋白的胞质尾区可能是 膜融合活性 小鼠白血病的C-末端片段 病毒Env蛋白（R肽）是病毒诱导的 膜融合 康潘斯博士将确定 R肽中的融合抑制所需的序列 活性，并测试假设，R的抑制活性 可溶性或膜锚定形式的肽具有作为 融合活性的显性负性抑制剂R肽可能会导致 包膜蛋白外部结构域构象的变化。 博士Compans先前获得的证据表明， 在F和HN蛋白之间发生，这是融合所必需的 然而，没有获得关于精确的信息。 这种互动的性质。 康潘斯博士将决定F和HN 与病毒体的表面物理结合和/或被感染 细胞，F蛋白是否经历构象变化， 激活聚变活动，以及这种变化是否需要其 与同型HN蛋白相互作用。 调查机制， F蛋白的哪些肽类似物作为高度特异性的抑制剂 人类副流感病毒的融合活性。

The objective of this project is to investigate two novel findings concerning membrane fusion induced by retroviruses and paramyxoviruses. One specific aim will investigate the mechanism by which sequences in the cytoplasmic tail of viral glycoproteins can be a major determinant of membrane fusion activity. The C-terminal segment of the murine leukemia virus Env protein (the R peptide) is a potent inhibitor of virus-induced membrane fusion. Dr Compans will determine the precise amino acid sequences in the R peptide which are required for its fusion-inhibitory activity, and test the hypothesis that the inhibitory activity of the R peptide in a soluble or membrane-anchored form have an effect as a dominant negative inhibitor of fusion activity R peptide may cause a change in the conformation of the external domain of the envelope protein. Dr. Compans previously obtained evidence that a type-specific interaction occurs between the F and HN proteins which is essential for the fusion activity however, no information has been obtained about the precise nature of this interaction. Dr. Compans will determine whether F and HN are physically associated ont he surfaces of virions and/or infected cells, whether the F protein undergoes a conformational change which activates fusion activity, and whether this change requires its interaction with a homotypic HN protein. Investigate the mechanism by which peptide analogs of the F proteins act as highly specific inhibitors of the fusion activity of human parainfluenza viruses.