TY  - EJOU
AU  - Ferraresi, Matteo 
AU  - Pezzi, Giulia 
AU  - Beltrami, Silvia 
AU  - Cianci, Giorgia 
AU  - Maini, Gloria 
AU  - Liboni, Alessia 
AU  - Baroni, Marcello 
AU  - Bortolotti, Daria 
AU  - Schiuma, Giovanna 
AU  - Rizzo, Sabrina 
AU  - Strazzabosco, Giovanni 

TI  - Emerging viral infections: role of flavivirus NS1-mediated rewiring of PRR signaling
T2  - European Cytokine Network

PY  - 
VL  - 
IS  - 
SN  - 1952-4005

AB  - 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 linked to inflammatory signaling, particularly through TLR4. At the cytosolic level, NS1 from DENV, WNV, and ZIKV disrupts RIG-I/MDA5–MAVS signaling and weakens IFN-β induction. NS1 also affects inflammasome pathways: DENV promotes IL-1β release through a CD14-dependent mechanism, ZIKV suppresses cGAS-mediated antiviral signaling, and JEV promotes NLRP3 inflammasome assembly. Overall, NS1 selectively dampens interferon-mediated antiviral defenses while sustaining or enhancing inflammation, contributing to endothelial dysfunction, neuroinflammation, and severe disease.
KW  - Flavivirus; nonstructural protein 1 (NS1); pattern recognition receptor (PRR) signaling modulation; antiviral immunity; inflammation

DO  - 10.32604/ecn.2026.083049