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Correlative multi-scale cryo-imaging unveils SARS-CoV-2 assembly and egress

Author

Listed:
  • Luiza Mendonça

    (University of Oxford)

  • Andrew Howe

    (Diamond Light Source, Harwell Science and Innovation Campus)

  • James B. Gilchrist

    (Diamond Light Source, Harwell Science and Innovation Campus)

  • Yuewen Sheng

    (Diamond Light Source, Harwell Science and Innovation Campus)

  • Dapeng Sun

    (University of Pittsburgh, Pittsburgh)

  • Michael L. Knight

    (University of Oxford)

  • Laura C. Zanetti-Domingues

    (Rutherford Appleton Laboratory)

  • Benji Bateman

    (Rutherford Appleton Laboratory)

  • Anna-Sophia Krebs

    (University of Oxford)

  • Long Chen

    (University of Oxford)

  • Julika Radecke

    (Diamond Light Source, Harwell Science and Innovation Campus)

  • Vivian D. Li

    (University of Cambridge)

  • Tao Ni

    (University of Oxford)

  • Ilias Kounatidis

    (Diamond Light Source, Harwell Science and Innovation Campus)

  • Mohamed A. Koronfel

    (Diamond Light Source, Harwell Science and Innovation Campus)

  • Marta Szynkiewicz

    (Rutherford Appleton Laboratory)

  • Maria Harkiolaki

    (Diamond Light Source, Harwell Science and Innovation Campus)

  • Marisa L. Martin-Fernandez

    (Rutherford Appleton Laboratory)

  • William James

    (University of Oxford)

  • Peijun Zhang

    (University of Oxford
    Diamond Light Source, Harwell Science and Innovation Campus
    University of Pittsburgh, Pittsburgh)

Abstract

Since the outbreak of the SARS-CoV-2 pandemic, there have been intense structural studies on purified viral components and inactivated viruses. However, structural and ultrastructural evidence on how the SARS-CoV-2 infection progresses in the native cellular context is scarce, and there is a lack of comprehensive knowledge on the SARS-CoV-2 replicative cycle. To correlate cytopathic events induced by SARS-CoV-2 with virus replication processes in frozen-hydrated cells, we established a unique multi-modal, multi-scale cryo-correlative platform to image SARS-CoV-2 infection in Vero cells. This platform combines serial cryoFIB/SEM volume imaging and soft X-ray cryo-tomography with cell lamellae-based cryo-electron tomography (cryoET) and subtomogram averaging. Here we report critical SARS-CoV-2 structural events – e.g. viral RNA transport portals, virus assembly intermediates, virus egress pathway, and native virus spike structures, in the context of whole-cell volumes revealing drastic cytppathic changes. This integrated approach allows a holistic view of SARS-CoV-2 infection, from the whole cell to individual molecules.

Suggested Citation

  • Luiza Mendonça & Andrew Howe & James B. Gilchrist & Yuewen Sheng & Dapeng Sun & Michael L. Knight & Laura C. Zanetti-Domingues & Benji Bateman & Anna-Sophia Krebs & Long Chen & Julika Radecke & Vivian, 2021. "Correlative multi-scale cryo-imaging unveils SARS-CoV-2 assembly and egress," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24887-y
    DOI: 10.1038/s41467-021-24887-y
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