Flavivirus Nonstructural Protein 1‑Driven Coagulation via Tissue Factor-Bearing Microvesicles: A Pilot Study.

Flaviviruses, such as dengue and West Nile, cause diverse clinical symptoms and trigger varied clinical outcomes, partly driven by the secreted nonstructural sNS1 protein (sNS1). This study examined how sNS1 from neurotropic and hemorrhagic flaviviruses affects coagulation and inflammation using human monocytic (THP-1) cells. sNS1 from neurotropic viruses (e.g., West Nile, Japanese encephalitis) increased tissue factor (TF) expression and the release of TF-bearing microvesicles, promoting procoagulant activity. In contrast, sNS1 from hemorrhagic viruses (e.g., dengue) showed anticoagulant effects. These divergent responses correlated with the virus-specific modulation of interleukin-6 (IL-6), suggesting that inflammation plays a central role in sNS1-mediated vascular changes. The findings identify sNS1 as a key virulence factor influencing flavivirus pathogenesis through hemostatic and immune pathways, offering a potential target for therapeutic intervention.