Orthobunyavirus ultrastructure and the curious tripodal glycoprotein spike

Thomas A. Bowden*, David Bitto, Angela McLees, Christelle Yeromonahos, Richard M. Elliott, Juha T. Huiskonen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)
2 Downloads (Pure)

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.

Original languageEnglish
Article numbere1003374
Number of pages10
JournalPLoS Pathogens
Volume9
Issue number5
DOIs
Publication statusPublished - 16 May 2013

Keywords

  • La-crosse-virus
  • Valley fever virus
  • EM structure determination
  • Membrane-fusion proteins
  • Electron-microscopy
  • Cryoelectron tomography
  • Envelope glycoprotein
  • Schmallenberg virus
  • Oropouche virus
  • Uukuniemi virus

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