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 . https://doi.org/10.1371/journal.ppat.1003374
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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