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

Nat Commun. 2021 Jul 30;12(1):4629. doi: 10.1038/s41467-021-24887-y.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COVID-19 / epidemiology
  • COVID-19 / immunology*
  • COVID-19 / virology
  • Chlorocebus aethiops
  • Cryoelectron Microscopy
  • Electron Microscope Tomography
  • Humans
  • Pandemics / prevention & control
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / physiology
  • SARS-CoV-2 / ultrastructure
  • Vero Cells
  • Virus Assembly / immunology*
  • Virus Assembly / physiology
  • Virus Release / immunology*
  • Virus Release / physiology
  • Virus Replication / immunology*
  • Virus Replication / physiology