1. Differential susceptibility of human motor neurons to infection with Usutu and West Nile virus.
- Author
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Marshall, Eleanor M., Bauer, Lisa, Nelemans, Tessa, Sooksawasdi Na Ayudhya, Syriam, Benavides, Feline, Lanko, Kristina, de Vrij, Femke M. S., Kushner, Steven A., Koopmans, Marion, van Riel, Debby, and Rockx, Barry
- Subjects
WEST Nile fever ,INDUCED pluripotent stem cells ,WEST Nile virus ,MOTOR neurons ,ACUTE flaccid paralysis - Abstract
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. Brief summary: West Nile virus, but not Usutu virus, can productively infect human motor neurons as a possible route of neuroinvasion. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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