Acidic pH-Induced Conformations and LAMP1 Binding of the Lassa Virus Glycoprotein Spike

PLoS Pathogens

Thomas A. Bowden¹  Marie-Laure Parsy¹  C. Alistair Siebert¹  Sai Li¹  Juha T. Huiskonen¹  Zhaoyang Sun¹  Rhys Pryce¹  Wolfgang Garten²  Sarah K. Fehling²  Katrin Schlie²  Thomas Strecker² 

[1] Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom;Institute of Virology, Philipps Universität Marburg, Marburg, Germany

关键词: Viral structure;    Virions;    Virus glycoproteins;    Crystal structure;    Lassa virus;    Membrane fusion;    Glycoproteins;    Arenaviruses;   

DOI  :  10.1371/journal.ppat.1005418

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY