title: Orthobunyavirus ultrastructure and the curious tripodal glycoprotein spike.
abstract: 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.
authors.affiliation: Oxford Particle Imaging Centre, Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bowden
authors.forename: David
authors.initials: D
authors.lastname: Bitto
authors.forename: Angela
authors.initials: A
authors.lastname: McLees
authors.forename: Christelle
authors.initials: C
authors.lastname: Yeromonahos
authors.forename: Richard M
authors.initials: RM
authors.lastname: Elliott
authors.forename: Juha T
authors.initials: JT
authors.lastname: Huiskonen
mesh_terms: D000818:Animals; D002042:Bunyamwera virus / Q000378:metabolism / Q000648:ultrastructure*; D002460:Cell Line; D006224:Cricetinae; D006023:Glycoproteins / Q000737:chemistry / Q000648:ultrastructure*; D006801:Humans; D020836:Protein Structure, Quaternary; D015678:Viral Structural Proteins / Q000378:metabolism / Q000648:ultrastructure*; D014771:Virion / Q000378:metabolism / Q000648:ultrastructure*
chemical_list: D006023:Glycoproteins; D015678:Viral Structural Proteins