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Cited by 33Viral Infections and Outbreaks ResearchAdvanced Electron Microscopy Techniques and ApplicationsVirology and Viral Diseases

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Intracellular Ebola virus nucleocapsid assembly revealed by in situ cryo-electron tomography

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Watanabe, Reika, Zyla, Dawid, Parekh, Diptiben, Hong, Connor, Jones, Ying, Schendel, Sharon L., Wan, William, Castillon, Guillaume, Saphire, Erica Ollmann·2024·Cell
DOI 10.1016/j.cell.2024.08.044PMC PMC11455616

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Abstract

Filoviruses, including the Ebola and Marburg viruses, cause hemorrhagic fevers with up to 90% lethality. The viral nucleocapsid is assembled by polymerization of the nucleoprotein (NP) along the viral genome, together with the viral proteins VP24 and VP35. We employed cryo-electron tomography of cells transfected with viral proteins and infected with model Ebola virus to illuminate assembly intermediates, as well as a 9 Å map of the complete intracellular assembly. This structure reveals a previously unresolved third and outer layer of NP complexed with VP35. The intrinsically disordered region, together with the C-terminal domain of this outer layer of NP, provides the constant width between intracellular nucleocapsid bundles and likely functions as a flexible tether to the viral matrix protein in the virion. A comparison of intracellular nucleocapsids with prior in-virion nucleocapsid structures reveals that the nucleocapsid further condenses vertically in the virion. The interfaces responsible for nucleocapsid assembly are highly conserved and offer targets for broadly effective antivirals.

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Metadata

Authors
Watanabe, R., Zyla, D., Parekh, D., Hong, C., Jones, Y., Schendel, S. L., Wan, W., Castillon, G., & Saphire, E. O.
Affiliations
  • La Jolla Institute for Immunology (US)
  • University of California San Diego (US)
  • Vanderbilt University (US)
Corresponding author
Saphire, Erica Ollmann
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2024-10
Volume
187
Issue
20
Pages
5587-5603.e19
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2024.08.044
PMC
PMC11455616
OpenAlex
W4402557382
Cited by
33
References
2
Citations by year
2026: 11 · 2025: 16 · 2024: 6
FWCI
11.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion, cc-by-nc)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
Funders
National Institutes of Health
Topics
  • Health Sciences › Medicine › Infectious Diseases › Viral Infections and Outbreaks Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
  • Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Keywords
Ebola virus, nucleocapsid assembly, nucleocapsid protein, VP35, VP24, filoviruses, cryo-electron tomography, intrinsically disordered regions, viral matrix protein, antiviral drug targets
MeSH terms
Animals, Chlorocebus aethiops, Humans, Models, Molecular, Nucleoproteins, Viral Proteins, Virion, Virus Assembly, Hemorrhagic Fever, Ebola, Nucleocapsid, Nucleocapsid Proteins, Cryoelectron Microscopy, Ebolavirus, Electron Microscope Tomography

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