Orthobunyavirus Ultrastructure and the Curious Tripodal Glycoprotein Spike

PLoS Pathogens

Christelle Yeromonahos¹  David Bitto¹  Juha T. Huiskonen¹  Richard M. Elliott²  Thomas A. Bowden²  Angela McLees² 

[1] Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, Fife, Scotland, United Kingdom;Oxford Particle Imaging Centre, Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom

关键词: Glycoproteins;    Viral structure;    Virions;    Virus glycoproteins;    Bunyaviruses;    Cell fusion;    Symmetry;    Host cells;   

DOI  :  10.1371/journal.ppat.1003374

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The genus Orthobunyavirus within the family Bunyaviridae constitutes an expanding group of emerging viruses, which threaten human and animal health. Despite the medical importance, little is known about orthobunyavirus structure, a prerequisite for understanding virus assembly and entry. Here, using electron cryo-tomography, we report the ultrastructure of Bunyamwera virus, the prototypic member of this genus. Whilst Bunyamwera virions are pleomorphic in shape, they display a locally ordered lattice of glycoprotein spikes. Each spike protrudes 18 nm from the viral membrane and becomes disordered upon introduction to an acidic environment. Using sub-tomogram averaging, we derived a three-dimensional model of the trimeric pre-fusion glycoprotein spike to 3-nm resolution. The glycoprotein spike consists mainly of the putative class-II fusion glycoprotein and exhibits a unique tripod-like arrangement. Protein–protein contacts between neighbouring spikes occur at membrane-proximal regions and intra-spike contacts at membrane-distal regions. This trimeric assembly deviates from previously observed fusion glycoprotein arrangements, suggesting a greater than anticipated repertoire of viral fusion glycoprotein oligomerization. Our study provides evidence of a pH-dependent conformational change that occurs during orthobunyaviral entry into host cells and a blueprint for the structure of this group of emerging pathogens.

【 授权许可】

CC BY