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Cited by 24Virology and Viral DiseasesCellular transport and secretionViral Infections and Vectors

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Organisation of the orthobunyavirus tripodal spike and the structural changes induced by low pH and K+ during entry

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Hover, Samantha, Charlton, Frank W., Hellert, Jan, Swanson, Jessica J., Mankouri, Jamel, Barr, John N., Fontana, Juan·2023·Nature Communications
DOI 10.1038/s41467-023-41205-wPMC PMC10514341

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Abstract

Following endocytosis, enveloped viruses employ the changing environment of maturing endosomes as cues to promote endosomal escape, a process often mediated by viral glycoproteins. We previously showed that both high [K + ] and low pH promote entry of Bunyamwera virus (BUNV), the prototypical bunyavirus. Here, we use sub-tomogram averaging and AlphaFold, to generate a pseudo-atomic model of the whole BUNV glycoprotein envelope. We unambiguously locate the Gc fusion domain and its chaperone Gn within the floor domain of the spike. Furthermore, viral incubation at low pH and high [K + ], reminiscent of endocytic conditions, results in a dramatic rearrangement of the BUNV envelope. Structural and biochemical assays indicate that pH 6.3/K + in the absence of a target membrane elicits a fusion-capable triggered intermediate state of BUNV GPs; but the same conditions induce fusion when target membranes are present. Taken together, we provide mechanistic understanding of the requirements for bunyavirus entry.

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Metadata

Authors
Hover, S., Charlton, F. W., Hellert, J., Swanson, J. J., Mankouri, J., Barr, J. N., & Fontana, J.
Affiliations
  • University of Leeds (GB)
  • Leibniz Institute of Virology (LIV) (DE)
Corresponding author
  • Mankouri, Jamel
  • Barr, John N.
  • Fontana, Juan
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2023-09-21
Volume
14
Issue
1
Pages
5885-5885
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-023-41205-w
PMC
PMC10514341
OpenAlex
W4386923313
Cited by
24
References
2
Citations by year
2026: 9 · 2025: 8 · 2024: 4 · 2023: 3
FWCI
4.96
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Desy Publications Database (Deutsches Elektronen-Synchrotron DESY) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DESY Publication Database (PUBDB) (Deutsches Elektronen-Synchrotron)
Funders
  • Academy of Medical Sciences (SBF002\1029)
  • Human Frontier Science Program (RGP0040/2019)
  • RCUK | MRC | Medical Research Foundation (MR/T016159/1)
  • Wellcome Trust (108466/Z/15/Z, 090932/Z/09/Z, 221524/Z/20/Z, WT104918MA)
  • RCUK | Biotechnology and Biological Sciences Research Council (BB/P001459/1)
  • University of Leeds (University Academic Fellow scheme)
Topics
  • Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
Keywords
Bunyamwera virus, Orthobunyavirus, viral entry, endosomal escape, low pH, potassium ions, membrane fusion, endocytosis
MeSH terms
Biological Assay, Bunyamwera virus, Cues, Hydrogen-Ion Concentration, Orthobunyavirus

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