@Article{ecn.2026.083049,
AUTHOR = {Matteo Ferraresi, Giulia Pezzi, Silvia Beltrami, Giorgia Cianci, Gloria Maini, Alessia Liboni, Marcello Baroni, Daria Bortolotti, Giovanna Schiuma, Sabrina Rizzo, Giovanni Strazzabosco},
TITLE = {Emerging viral infections: role of flavivirus NS1-mediated rewiring of PRR signaling},
JOURNAL = {European Cytokine Network},
VOLUME = {},
YEAR = {},
NUMBER = {},
PAGES = {{pages}},
URL = {http://www.techscience.com/ECN/online/detail/27307},
ISSN = {1952-4005},
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 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.},
DOI = {10.32604/ecn.2026.083049}
}