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Open Access 03-01-2024 | SARS-CoV-2

SARS-CoV and SARS-CoV-2 display limited neuronal infection and lack the ability to transmit within synaptically connected axons in stem cell–derived human neurons

Authors: Jasmina M. Luczo, Sarah J. Edwards, Katie Ardipradja, Willy W. Suen, Gough G. Au, Glenn A. Marsh, Nathan Godde, Christina L. Rootes, John Bingham, Vinod Sundaramoorthy

Published in: Journal of NeuroVirology | Issue 1/2024

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Abstract

Sarbecoviruses such as SARS and SARS-CoV-2 have been responsible for two major outbreaks in humans, the latter resulting in a global pandemic. While sarbecoviruses primarily cause an acute respiratory infection, they have been shown to infect the nervous system. However, mechanisms of sarbecovirus neuroinvasion and neuropathogenesis remain unclear. In this study, we examined the infectivity and trans-synaptic transmission potential of the sarbecoviruses SARS and SARS-CoV-2 in human stem cell–derived neural model systems. We demonstrated limited ability of sarbecoviruses to infect and replicate in human stem cell–derived neurons. Furthermore, we demonstrated an inability of sarbecoviruses to transmit between synaptically connected human stem cell–derived neurons. Finally, we determined an absence of SARS-CoV-2 infection in olfactory neurons in experimentally infected ferrets. Collectively, this study indicates that sarbecoviruses exhibit low potential to infect human stem cell–derived neurons, lack an ability to infect ferret olfactory neurons, and lack an inbuilt molecular mechanism to utilise retrograde axonal trafficking and trans-synaptic transmission to spread within the human nervous system.
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Metadata
Title
SARS-CoV and SARS-CoV-2 display limited neuronal infection and lack the ability to transmit within synaptically connected axons in stem cell–derived human neurons
Authors
Jasmina M. Luczo
Sarah J. Edwards
Katie Ardipradja
Willy W. Suen
Gough G. Au
Glenn A. Marsh
Nathan Godde
Christina L. Rootes
John Bingham
Vinod Sundaramoorthy
Publication date
03-01-2024
Publisher
Springer International Publishing
Published in
Journal of NeuroVirology / Issue 1/2024
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI
https://doi.org/10.1007/s13365-023-01187-3

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