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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.

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 :
Luczo JM
Edwards SJ
Ardipradja K
Suen WW
Au GG
Marsh GA
Godde N
Rootes CL
Bingham J
Sundaramoorthy V
Source :
Journal of neurovirology [J Neurovirol] 2024 Feb; Vol. 30 (1), pp. 39-51. Date of Electronic Publication: 2024 Jan 03.
Publication Year :
2024

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.<br /> (© 2023. The Author(s).)

Details

Language :
English
ISSN :
1538-2443
Volume :
30
Issue :
1
Database :
MEDLINE
Journal :
Journal of neurovirology
Publication Type :
Academic Journal
Accession number :
38172412
Full Text :
https://doi.org/10.1007/s13365-023-01187-3