Neurovirulence of Usutu virus in human fetal organotypic brain slice cultures partially resembles Zika and West Nile virus.

Autor: Marshall EM; Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands., Rashidi AS; Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.; HerpeslabNL of the Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands., van Gent M; Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.; HerpeslabNL of the Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands., Rockx B; Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands. b.rockx@erasmusmc.nl., Verjans GMGM; Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands. g.verjans@erasmusmc.nl.; HerpeslabNL of the Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands. g.verjans@erasmusmc.nl.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Aug 29; Vol. 14 (1), pp. 20095. Date of Electronic Publication: 2024 Aug 29.
DOI: 10.1038/s41598-024-71050-w
Abstrakt: Usutu (USUV), West Nile (WNV), and Zika virus (ZIKV) are neurotropic arthropod-borne viruses (arboviruses) that cause severe neurological disease in humans. However, USUV-associated neurological disease is rare, suggesting a block in entry to or infection of the brain. We determined the replication, cell tropism and neurovirulence of these arboviruses in human brain tissue using a well-characterized human fetal organotypic brain slice culture model. Furthermore, we assessed the efficacy of interferon-β and 2'C-methyl-cytidine, a synthetic nucleoside analogue, in restricting viral replication. All three arboviruses replicated within the brain slices, with WNV reaching the highest titers, and all primarily infected neuronal cells. USUV- and WNV-infected cells exhibited a shrunken morphology, not associated with detectable cell death. Pre-treatment with interferon-β inhibited replication of all arboviruses, while 2'C-methyl-cytidine reduced only USUV and ZIKV titers. Collectively, USUV can infect human brain tissue, showing similarities in tropism and neurovirulence as WNV and ZIKV. These data suggest that a blockade to infection of the human brain may not be the explanation for the low clinical incidence of USUV-associated neurological disease. However, USUV replicated more slowly and to lower titers than WNV, which could help to explain the reduced severity of neurological disease resulting from USUV infection.
(© 2024. The Author(s).)
Databáze: MEDLINE
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