Li Sai, Sun Zhaoyang, Pryce Rhys, Parsy Marie-Laure, Fehling Sarah K, Schlie Katrin, Siebert C Alistair, Garten Wolfgang, Bowden Thomas A, Strecker Thomas, Huiskonen Juha T
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Institute of Virology, Philipps Universität Marburg, Marburg, Germany.
PLoS Pathog. 2016 Feb 5;12(2):e1005418. doi: 10.1371/journal.ppat.1005418. eCollection 2016 Feb.
Lassa virus is an enveloped, bi-segmented RNA virus and the most prevalent and fatal of all Old World arenaviruses. Virus entry into the host cell is mediated by a tripartite surface spike complex, which is composed of two viral glycoprotein subunits, GP1 and GP2, and the stable signal peptide. Of these, GP1 binds to cellular receptors and GP2 catalyzes fusion between the viral envelope and the host cell membrane during endocytosis. The molecular structure of the spike and conformational rearrangements induced by low pH, prior to fusion, remain poorly understood. Here, we analyzed the three-dimensional ultrastructure of Lassa virus using electron cryotomography. Sub-tomogram averaging yielded a structure of the glycoprotein spike at 14-Å resolution. The spikes are trimeric, cover the virion envelope, and connect to the underlying matrix. Structural changes to the spike, following acidification, support a viral entry mechanism dependent on binding to the lysosome-resident receptor LAMP1 and further dissociation of the membrane-distal GP1 subunits.
拉沙病毒是一种有包膜的双节段RNA病毒，是所有旧大陆沙粒病毒中最常见且致命的。病毒进入宿主细胞是由一个三聚体表面刺突复合体介导的，该复合体由两个病毒糖蛋白亚基GP1和GP2以及稳定信号肽组成。其中，GP1与细胞受体结合，GP2在内吞过程中催化病毒包膜与宿主细胞膜之间的融合。在融合之前，刺突的分子结构以及低pH诱导的构象重排仍知之甚少。在此，我们使用电子冷冻断层扫描分析了拉沙病毒的三维超微结构。亚断层平均法得到了分辨率为14埃的糖蛋白刺突结构。刺突是三聚体，覆盖病毒粒子包膜，并与下面的基质相连。酸化后刺突的结构变化支持一种依赖于与溶酶体驻留受体LAMP1结合以及膜远端GP1亚基进一步解离的病毒进入机制。
