Orthobunyavirus Ultrastructure and the Curious Tripodal Glycoprotein Spike

Autor: Bowden, Thomas, Bitto, David, McLees, Angela, Yeromonahos, Christelle, Elliott, Richard, Huiskonen, Juha, Pierson, Ted
Přispěvatelé: Centre for Virus Research, MRC - University of Glasgow Centre for Virus Research, Laboratoire de rhéologie (LR), Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique de Grenoble (INPG)-Université Joseph Fourier - Grenoble 1 (UJF), The Wellcome Trust, University of St Andrews. School of Biology, University of St Andrews. Biomedical Sciences Research Complex
Rok vydání: 2013
Předmět:
Macromolecular Assemblies
Membrane-fusion proteins
medicine.disease_cause
Electron-microscopy
Biochemistry
Protein structure
Cricetinae
La-crosse-virus
Biology (General)
ComputingMilieux_MISCELLANEOUS
chemistry.chemical_classification
0303 health sciences
Cell fusion
[CHIM.MATE]Chemical Sciences/Material chemistry
Entry into host
Valley fever virus
Cell biology
[CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry
Infectious Diseases
Oropouche virus
Medicine
QR355 Virology
Research Article
QH301-705.5
[PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph]
Immunology
Biophysics
Envelope glycoprotein
EM structure determination
Biology
Microbiology
Orthobunyavirus
Cell Line
03 medical and health sciences
SDG 3 - Good Health and Well-being
Bunyamwera virus
Virology
Genetics
medicine
Animals
Humans
Protein Structure
Quaternary
Molecular Biology
Glycoproteins
030304 developmental biology
QR355
Viral Structural Proteins
030306 microbiology
Virion
Lipid bilayer fusion
Uukuniemi virus
RC581-607
Viral membrane
biology.organism_classification
Schmallenberg virus
[INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation
chemistry
Cryoelectron tomography
Parasitology
[PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph]
Immunologic diseases. Allergy
Glycoprotein
Zdroj: PLoS Pathogens
PLoS Pathogens, Public Library of Science, 2013, 9 (5), ⟨10.1371/journal.ppat.1003374⟩
PLoS Pathogens, Vol 9, Iss 5, p e1003374 (2013)
ISSN: 1553-7374
1553-7366
DOI: 10.1371/journal.ppat.1003374
Popis: 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.
Author Summary Orthobunyaviruses comprise a group of emerging arboviruses within the Bunyaviridae, the largest family of membrane-containing viruses. In spite of the continued medical impact upon human and animal health, little is known about orthobunyavirus structure or the process of host cell entry. Here, we address this paucity of information through electron cryo-microscopy analysis of Bunyamwera virus, the prototypic representative of this genus. We reveal that Bunyamwera virions are pleomorphic and display locally-ordered lattices of viral glycoprotein spikes on the envelope surface. The three-dimensional structure of the glycoprotein spike was resolved to 3.0-nm resolution. The spike is composed of the attachment and fusion glycoproteins and comprises a unique tripodal organization. This glycoprotein arrangement contrasts those observed in other virus families. Consistent with the established pH-dependent mechanism of membrane fusion during host cell entry, we provide evidence for the disruption of this tripodal assembly upon exposure to acidic environments. These data constitute a blueprint for orthobunyavirus architecture and support a case for broadened structural diversity within the Bunyaviridae family.
Databáze: OpenAIRE
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