Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, USA.
J Virol. 2014 Apr;88(8):3925-41. doi: 10.1128/JVI.03741-13. Epub 2014 Jan 22.
Paramyxoviruses are a large family of membrane-enveloped negative-stranded RNA viruses causing important diseases in humans and animals. Two viral integral membrane glycoproteins (fusion [F] and attachment [HN, H, or G]) mediate a concerted process of host receptor recognition, followed by the fusion of viral and cellular membranes, resulting in viral nucleocapsid entry into the cytoplasm. However, the sequence of events that closely links the timing of receptor recognition by HN, H, or G and the "triggering" interaction of the attachment protein with F is unclear. F activation results in F undergoing a series of irreversible conformational rearrangements to bring about membrane merger and virus entry. By extensive study of properties of multiple paramyxovirus HN proteins, we show that key features of F activation, including the F-activating regions of HN proteins, flexibility within this F-activating region, and changes in globular head-stalk interactions are highly conserved. These results, together with functionally active "headless" mumps and Newcastle disease virus HN proteins, provide insights into the F-triggering process. Based on these data and very recently published data for morbillivirus H and henipavirus G proteins, we extend our recently proposed "stalk exposure model" to other paramyxoviruses and propose an "induced fit" hypothesis for F-HN/H/G interactions as conserved core mechanisms of paramyxovirus-mediated membrane fusion.
Paramyxoviruses are a large family of membrane-enveloped negative-stranded RNA viruses causing important diseases in humans and animals. Two viral integral membrane glycoproteins (fusion [F] and attachment [HN, H, or G]) mediate a concerted process of host receptor recognition, followed by the fusion of viral and cellular membranes. We describe here the molecular mechanism by which HN activates the F protein such that virus-cell fusion is controlled and occurs at the right time and the right place. We extend our recently proposed "stalk exposure model" first proposed for parainfluenza virus 5 to other paramyxoviruses and propose an "induced fit" hypothesis for F-HN/H/G interactions as conserved core mechanisms of paramyxovirus-mediated membrane fusion.
副黏液病毒是一个大的膜包被的负链 RNA 病毒家族，导致人类和动物的重要疾病。两种病毒的完整膜糖蛋白（融合[F]和附着[HN、H 或 G]）介导宿主受体识别的协同过程，随后是病毒和细胞膜的融合，导致病毒核衣壳进入细胞质。然而，HN、H 或 G 识别受体的时间顺序以及附着蛋白与 F 的“触发”相互作用紧密联系的事件序列尚不清楚。F 的激活导致 F 经历一系列不可逆的构象重排，从而导致膜融合和病毒进入。通过对多种副黏液病毒 HN 蛋白特性的广泛研究，我们表明 F 激活的关键特征，包括 HN 蛋白的 F 激活区域、该 F 激活区域内的灵活性以及球状头茎相互作用的变化，高度保守。这些结果，以及功能活性的“无头”腮腺炎病毒和新城疫病毒 HN 蛋白，提供了对 F 触发过程的深入了解。基于这些数据以及最近发表的关于麻疹病毒 H 和亨德拉病毒 G 蛋白的数据，我们将我们最近提出的“茎干暴露模型”扩展到其他副黏液病毒，并提出了 F-HN/H/G 相互作用的“诱导契合”假说，作为副黏液病毒介导的膜融合的保守核心机制。
副黏液病毒是一个大的膜包被的负链 RNA 病毒家族，导致人类和动物的重要疾病。两种病毒的完整膜糖蛋白（融合[F]和附着[HN、H 或 G]）介导宿主受体识别的协同过程，随后是病毒和细胞膜的融合。我们在这里描述了 HN 激活 F 蛋白的分子机制，从而控制病毒细胞融合，并在正确的时间和地点发生。我们将我们最近提出的“茎干暴露模型”扩展到其他副黏液病毒，并提出了 F-HN/H/G 相互作用的“诱导契合”假说，作为副黏液病毒介导的膜融合的保守核心机制。
