Differential susceptibility of human motor neurons to infection with Usutu and West Nile virus.
Antiviral response
Flavivirus
Interferon
Motor neurons
Neuroinvasion
Usutu virus
West Nile acute flaccid paralysis
West Nile virus
Journal
Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974
Informations de publication
Date de publication:
27 Sep 2024
27 Sep 2024
Historique:
received:
22
05
2024
accepted:
09
09
2024
medline:
28
9
2024
pubmed:
28
9
2024
entrez:
28
9
2024
Statut:
epublish
Résumé
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. West Nile virus, but not Usutu virus, can productively infect human motor neurons as a possible route of neuroinvasion.
Autres résumés
Type: plain-language-summary
(eng)
West Nile virus, but not Usutu virus, can productively infect human motor neurons as a possible route of neuroinvasion.
Identifiants
pubmed: 39334427
doi: 10.1186/s12974-024-03228-y
pii: 10.1186/s12974-024-03228-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
236Subventions
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek
ID : NWA.1160.1S.210
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek
ID : OCENW.XS22.2.045
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek
ID : NWA.1160.1S.210
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek
ID : NWA.1160.1S.210
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek
ID : NWA.1160.1S.210
Organisme : Europäische Gesellschaft für klinische Mikrobiologie und Infektionskrankheiten
ID : ESCMID Research Grant
Organisme : Erasmus Medisch Centrum
ID : Human Disease Model Award
Organisme : ZonMw
ID : 10250022110002
Pays : Netherlands
Organisme : ZonMw
ID : 10250022110002
Pays : Netherlands
Organisme : Ministerie van Onderwijs, Cultuur en Wetenschappen
ID : 024.003.001
Organisme : Ministerie van Onderwijs, Cultuur en Wetenschappen
ID : 024.003.001
Informations de copyright
© 2024. The Author(s).
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