Differential susceptibility of human motor neurons to infection with Usutu and West Nile virus.

Autor: Marshall EM; Department of Viroscience, Erasmus Medical Center, Dr. Molewaterplein 40, Rotterdam, 3015 GD, The Netherlands., Bauer L; Department of Viroscience, Erasmus Medical Center, Dr. Molewaterplein 40, Rotterdam, 3015 GD, The Netherlands., Nelemans T; Department of Medical Microbiology, Leiden University Medical Centre, Leiden, the Netherlands., Sooksawasdi Na Ayudhya S; Department of Viroscience, Erasmus Medical Center, Dr. Molewaterplein 40, Rotterdam, 3015 GD, The Netherlands.; Faculty of Veterinary Science, Prince of Songkla University, Songkhla, Thailand., Benavides F; Department of Viroscience, Erasmus Medical Center, Dr. Molewaterplein 40, Rotterdam, 3015 GD, The Netherlands., Lanko K; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands., de Vrij FMS; Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands., Kushner SA; Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands.; Department of Psychiatry, Columbia University Medical Center, New York, NY, USA., Koopmans M; Department of Viroscience, Erasmus Medical Center, Dr. Molewaterplein 40, Rotterdam, 3015 GD, The Netherlands., van Riel D; Department of Viroscience, Erasmus Medical Center, Dr. Molewaterplein 40, Rotterdam, 3015 GD, The Netherlands., Rockx B; Department of Viroscience, Erasmus Medical Center, Dr. Molewaterplein 40, Rotterdam, 3015 GD, The Netherlands. b.rockx@erasmusmc.nl.
Jazyk: angličtina
Zdroj: Journal of neuroinflammation [J Neuroinflammation] 2024 Sep 27; Vol. 21 (1), pp. 236. Date of Electronic Publication: 2024 Sep 27.
DOI: 10.1186/s12974-024-03228-y
Abstrakt: West Nile virus (WNV) and Usutu virus (USUV) are closely related flaviviruses with differing capacities to cause neurological disease in humans. WNV is thought to use a transneural route of neuroinvasion along motor neurons and causes severe motor deficits. The potential for use of transneural routes of neuroinvasion by USUV has not been investigated experimentally, and evidence from the few clinical case reports of USUV-associated neuroinvasive disease is lacking. We hypothesised that, compared with WNV, USUV is less able to infect motor neurons, and therefore determined the susceptibility of human induced pluripotent stem cell (iPSC)-derived spinal cord motor neurons to infection. Both viruses could grow to high titres in iPSC-derived neural cultures. However, USUV could not productively infect motor neurons due to restriction by the antiviral response, which was not induced upon WNV infection. Inhibition of the antiviral response allowed for widespread infection and transportation of USUV along motor neurons within a compartmented culture system. These results show a stark difference in the ability of these two viruses to evade initiation of intrinsic antiviral immunity. Our data suggests that USUV cannot infect motor neurons in healthy individuals but in case of immunodeficiency may pose a risk for motor-related neurological disease and transneural invasion.
(© 2024. The Author(s).)
Databáze: MEDLINE
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