Galdiero Stefania, Falanga Annarita, Vitiello Mariateresa, Browne Helena, Pedone Carlo, Galdiero Massimiliano
Department of Biological Sciences, Division of Biostructures, University of Naples "Federico II", Naples, Italy.
J Biol Chem. 2005 Aug 5;280(31):28632-43. doi: 10.1074/jbc.M505196200. Epub 2005 Jun 2.
Infection of eukaryotic cells by enveloped viruses requires fusion between the viral envelope and the cellular plasma or endosomal membrane. The actual merging of the two membranes is mediated by viral envelope glycoproteins, which generally contain a highly hydrophobic region termed the fusion peptide. The entry of herpesviruses is mediated by three conserved proteins: glycoproteins B, H (gH), and L. However, how fusion is executed remains unknown. Herpes simplex virus type 1 gH exhibits features typical of viral fusion glycoproteins, and its ectodomain seems to contain a putative internal fusion peptide. Here, we have identified additional internal segments able to interact with membranes and to induce membrane fusion of large unilamellar vesicles. We have applied the hydrophobicity-at-interface scale proposed by Wimley and White (Wimley, W. C., and White, S. H. (1996) Nat. Struct. Biol. 3, 842-848) to identify six hydrophobic stretches within gH with a tendency to partition into the membrane interface, and four of them were able to induce membrane fusion. Experiments in which equimolar mixtures of gH peptides were used indicated that different fusogenic regions may act in a synergistic way. The functional and structural characterization of these segments suggests that herpes simplex virus type 1 gH possesses several fusogenic internal peptides that could participate in the actual fusion event.
包膜病毒感染真核细胞需要病毒包膜与细胞质膜或内体膜融合。这两种膜的实际融合由病毒包膜糖蛋白介导，这些糖蛋白通常含有一个称为融合肽的高度疏水区域。疱疹病毒的进入由三种保守蛋白介导：糖蛋白B、H（gH）和L。然而，融合是如何发生的仍不清楚。单纯疱疹病毒1型gH具有病毒融合糖蛋白的典型特征，其胞外域似乎含有一个假定的内部融合肽。在这里，我们鉴定出了其他能够与膜相互作用并诱导大单层囊泡膜融合的内部片段。我们应用了Wimley和White提出的界面疏水性标度（Wimley，W.C.，和White，S.H.（1996）《自然结构生物学》3，842 - 848）来鉴定gH内六个倾向于分配到膜界面的疏水片段，其中四个能够诱导膜融合。使用gH肽等摩尔混合物的实验表明，不同的融合区域可能以协同方式起作用。这些片段的功能和结构特征表明，单纯疱疹病毒1型gH拥有几个可能参与实际融合事件的融合内部肽。
