Differential properties of NS1 glycoproteins in West Nile and Usutu viruses
Abstract
West Nile virus (WNV) and Usutu virus (USUV) are neurotropic orthoflaviviruses of the Flaviviridae family, transmitted primarily by Culex mosquitoes and maintained in enzootic cycles involving birds. While WNV is a well-established human pathogen causing hundreds of neuroinvasive cases annually in Europe, USUV has emerged more recently, with fewer documented human infections but increasing evidence of neurovirulence. The viral nonstructural protein 1 (NS1) plays a central role in orthoflavivirus pathogenesis by modulating host immune responses, disrupting endothelial barrier integrity, and facilitating viral dissemination. However, the functional and biochemical properties of NS1 from WNV and USUV remain poorly characterized. We combined in vitro, in vivo, and clinical approaches to compare NS1 secretion, stability, and its impact on blood-brain barrier. Our results show that WNV NS1 is secreted at significantly higher levels, exhibits greater thermal stability, and disrupts brain endothelial barrier integrity in vitro. In contrast, USUV NS1 is secreted less efficiently, is slightly less stable, and does not compromise blood-brain barrier integrity, despite inducing distinct transcriptional responses in brain endothelial cells. In mice, WNV infection led to higher serum NS1 levels and stronger systemic inflammation than USUV. Clinically, WNV NS1 was detected mainly in patients with neurological symptoms, whereas USUV NS1 remained undetectable in all cases. Altogether, these findings reveal differential NS1 properties between these closely related viruses, with key implications for orthoflavivirus diagnosis and neurovirulence mechanisms.
Related
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- Identification of Usutu virus in blood donors as part of molecular screening for West Nile virus, France, 2023.
- Usutu virus promotes West Nile virus replication in Culex pipiens biotype molestus during simultaneous and sequential co-infections
- Quantifying the current and future risk of West Nile virus and Usutu virus in humans and horses across England and Wales using an R0-based suitability metric
BibTeX
@article{revel2026differential,
title = {{Differential properties of NS1 glycoproteins in West Nile and Usutu viruses}},
author = {Justine Revel and Jérémy Leroy and Stéphane Delbecq and Orianne Constant and Florent Henry Marty and Chaima Naili and Arthur Barthès and Anna Nagy and Jonas Schmidt-Chanasit and Dániel Cadar and Nor Yasmin Abd. Rahaman and Anne-Dominique Lajoix and Caroline Desmetz and Yannick Simonin},
journal = {Emerging microbes \& infections},
year = {2026},
month = may,
doi = {10.1080/22221751.2026.2667565},
url = {https://hal.science/hal-05769412v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Differential properties of NS1 glycoproteins in West Nile and Usutu viruses
AU - Justine Revel
AU - Jérémy Leroy
AU - Stéphane Delbecq
AU - Orianne Constant
AU - Florent Henry Marty
AU - Chaima Naili
AU - Arthur Barthès
AU - Anna Nagy
AU - Jonas Schmidt-Chanasit
AU - Dániel Cadar
AU - Nor Yasmin Abd. Rahaman
AU - Anne-Dominique Lajoix
AU - Caroline Desmetz
AU - Yannick Simonin
PY - 2026
DA - 2026/05/29
JO - Emerging microbes & infections
DO - 10.1080/22221751.2026.2667565
UR - https://hal.science/hal-05769412v1
AB - West Nile virus (WNV) and Usutu virus (USUV) are neurotropic orthoflaviviruses of the Flaviviridae family, transmitted primarily by Culex mosquitoes and maintained in enzootic cycles involving birds. While WNV is a well-established human pathogen causing hundreds of neuroinvasive cases annually in Europe, USUV has emerged more recently, with fewer documented human infections but increasing evidence of neurovirulence. The viral nonstructural protein 1 (NS1) plays a central role in orthoflavivirus pathogenesis by modulating host immune responses, disrupting endothelial barrier integrity, and facilitating viral dissemination. However, the functional and biochemical properties of NS1 from WNV and USUV remain poorly characterized. We combined in vitro, in vivo, and clinical approaches to compare NS1 secretion, stability, and its impact on blood-brain barrier. Our results show that WNV NS1 is secreted at significantly higher levels, exhibits greater thermal stability, and disrupts brain endothelial barrier integrity in vitro. In contrast, USUV NS1 is secreted less efficiently, is slightly less stable, and does not compromise blood-brain barrier integrity, despite inducing distinct transcriptional responses in brain endothelial cells. In mice, WNV infection led to higher serum NS1 levels and stronger systemic inflammation than USUV. Clinically, WNV NS1 was detected mainly in patients with neurological symptoms, whereas USUV NS1 remained undetectable in all cases. Altogether, these findings reveal differential NS1 properties between these closely related viruses, with key implications for orthoflavivirus diagnosis and neurovirulence mechanisms.
SN - 2222-1751
SN - 2222-1751
ER -