Orthobunyavirus ultrastructure and the curious tripodal glycoprotein spike
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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.
Bowden , T A , Bitto , D , McLees , A , Yeromonahos , C , Elliott , R M & Huiskonen , J T 2013 , ' Orthobunyavirus ultrastructure and the curious tripodal glycoprotein spike ' PLoS Pathogens , vol 9 , no. 5 , e1003374 . DOI: 10.1371/journal.ppat.1003374
Copyright: © 2013 Bowden et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. http://creativecommons.org/licenses/by/3.0/
DescriptionThis work was supported by the Wellcome Trust (090532/Z/09/Z; 089026/Z/09/Z to TAB; 079810 to RME) and by the Academy of Finland (130750 and 218080 to JTH).
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