病毒囊膜与宿主细胞膜的膜融合是囊膜病毒入侵的重要过程、病毒囊膜融合糖蛋白的一系列结构变化引发此过程。综述了Ⅱ类囊膜病毒、弹状病毒及疱疹病毒融合蛋白结构与功能研究的最新进展、介绍了软件分析并定位融合蛋白功能区域的方法。Ⅱ类病毒与Ⅰ类病毒融合蛋白的融合前结构不同、但融合后结构（发夹三聚体结构）相似。弹状病毒与疱疹病毒的融合蛋白集合了Ⅰ/Ⅱ类融合蛋白的某些特征、但其结构变化及融合过程各不相同、被归为新型融合蛋白。上述研究为基础设计的以病毒融合过程为靶标的抑制子、可为抗病毒新药的研制提供新思路。

Paramyxovirus might adopt a molecular mechanism of membrane fusion similar to that of other class I viruses in which the heptad repeat (HR) regions of fusion protein (F) HR1 and HR2 form a six-helix bundle structure inducing membrane fusion. In this study, we examined the structure and function of HR1 and HR2 from the avian paramyxovirus-2 (APMV-2) F protein. The study showed that APMV-2 HR1 and HR2 formed a stable six-helix bundle. Only a soluble APMV-2 HR2 peptide showed potent and specific virus-cell fusion inhibition activity. Cross-inhibiting activity with APMV-1 (Newcastle disease virus, NDV) was not found. A possible mechanism of membrane fusion inhibition by the paramyxovirus HR2 peptide is discussed.

It is emerging that enveloped viruses may adopt a unique entry/fusion mechanism; in paramyxoviruses, including Sendai virus (SeV), the attachment protein HN (or its homologue H or G) binds a cellular receptor which triggers conformational changes of its fusion protein, F. There are at least three conformations of the F protein in the current fusion model: the pre-fusion native conformation, the prehairpin intermediate conformation and the post-fusion coiled-coil conformation. The fusion mechanism of SeV, a member of the Paramyxoviridae family, has been well established and several structural and functional domains or modules have been proposed from studies of its F protein. However, biochemical and biophysical studies of the heptad-repeat (HR) regions (HR1 and HR2) have not been systematically carried out. HR1 and HR2 strongly interact with each other to form a stable six-helix coiled-coil bundle as the postfusion conformation. In this study, a single-chain HR1-linker-HR2 protein of SeV was prepared in an Escherichia coli expression system and biochemical and biophysical analyses showed it to form a typical six-helix coiled-coil bundle; its trigonal crystals diffracted X-rays to 2.5

囊膜病毒可能采用相似的病毒-宿主细胞膜融合机制，即病毒表面糖蛋白结合到宿主细胞受体后，启动了病毒融合蛋白的一系列构象变化，根据囊膜蛋白构象变化特征，囊膜病毒可采用两种以上的方式发生膜融合，并据此分为两类：型病毒膜融合和Ⅱ型病毒膜融合。Ⅱ型病毒膜融合以黄病毒为代表，其分子机制与Ⅰ型病毒膜融合不同，但不很清楚。而Ⅰ型病毒膜融合中，如艾滋病毒，流感病毒等，在囊膜蛋白变构形成稳定折叠的发夹三聚体结构时，拉近了两膜之间的距离，此过程释放出来的能量进一步促使两膜融合。膜融合使病毒蛋白及病毒RNA基因组释放到宿主细胞内而感染宿主。以上述研究为基础设计的C肽/N肽小分子抑制子，可以在病毒糖蛋白中间体构象形成的短时间内，高效、特异地竞争结合其配体，从而阻止糖蛋白的进一步折叠，达到抑制病毒入侵的目的，为病毒疾病的防治提供了新思路和策略。针对艾滋病毒设计的C肽、即T20或Enfuvirtide在临床应用效果很好。以艾滋病毒和流感病毒为例，主要对Ⅰ型病毒膜融合的研究进展进行了讨论。