SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography

Nature Communications
Steffen KleinPetr Chlanda

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID19 pandemic, is a highly pathogenic β-coronavirus. As other coronaviruses, SARS-CoV-2 is enveloped, replicates in the cytoplasm and assembles at intracellular membranes. Here, we structurally characterize the viral replication compartment and report critical insights into the budding mechanism of the virus, and the structure of extracellular virions close to their native state by in situ cryo-electron tomography and subtomogram averaging. We directly visualize RNA filaments inside the double membrane vesicles, compartments associated with viral replication. The RNA filaments show a diameter consistent with double-stranded RNA and frequent branching likely representing RNA secondary structures. We report that assembled S trimers in lumenal cisternae do not alone induce membrane bending but laterally reorganize on the envelope during virion assembly. The viral ribonucleoprotein complexes (vRNPs) are accumulated at the curved membrane characteristic for budding sites suggesting that vRNP recruitment is enhanced by membrane curvature. Subtomogram averaging shows that vRNPs are distinct cylindrical assemblies. We propose that the genome is ...Continue Reading

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Citations

Feb 13, 2021·Journal of Biological Rhythms·Jeffrey HaspelMartha Merrow
Feb 12, 2021·ACS Infectious Diseases·Kas SteutenMatthew Bogyo
Jan 23, 2021·Membranes·Jordana Muñoz-BasagoitiNuria Izquierdo-Useros
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Methods Mentioned

BETA
electron microscopy
PCR

Software Mentioned

Dynamo
cryo
CARE
MAPS
ImageJ
Tomo2Tomo
SerialEM
EMAN2
ChimeraX
Primer3

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