Matteo Ferraresi1, Giulia Pezzi1, Silvia Beltrami1, Giorgia Cianci1, Gloria Maini1, Alessia Liboni2, Marcello Baroni3, Daria Bortolotti1,*, Giovanna Schiuma1,*, Sabrina Rizzo1,#, Giovanni Strazzabosco1,#
European Cytokine Network, Vol.37, No.2, pp. 41-53, 2026, DOI:10.32604/ecn.2026.083049
- 30 June 2026
Abstract Flaviviruses, including Dengue, West Nile, Zika, and Japanese encephalitis viruses, are arthropod-borne RNA viruses that pose an increasing global health threat. This review summarizes the role of nonstructural protein 1 (NS1), a multifunctional glycoprotein found in intracellular and secreted forms, as a key regulator of innate immunity. NS1 modulates several pattern recognition receptor pathways, including TLRs, RLRs, SR-B1-related mechanisms, and inflammasome platforms, thereby altering cytokine and interferon responses. Its effects are virus- and context-dependent. WNV NS1 inhibits TLR3/TRIF signaling, reducing IRF3 activation, type I interferon production, and interferon-stimulated gene expression. In contrast, DENV NS1 is More >