Differential Properties of NS1 Glycoproteins in West Nile and Usutu Viruses.

. 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.