Submit

Login Login

Register Register

Home / Journals / ECN / Online First / doi:10.32604/ecn.2026.083049
Journal Menu
Special Issues
Table of Content

All issues

Online First

2026

2025

2024

2023

2022

2021

2020

2019

2018

2017

2016

2015

2014

2013

2012

2011

2010

2009

2008

2007

2006

2005

2004

2003

Past lssues

Open Access

REVIEW

Emerging viral infections: role of flavivirus NS1-mediated rewiring of PRR signaling

Matteo Ferraresi1, Giulia Pezzi1, Silvia Beltrami1, Giorgia Cianci1, Gloria Maini1, Alessia Liboni2, Marcello Baroni3, Daria Bortolotti1,*, Giovanna Schiuma1,*, Sabrina Rizzo1,#, Giovanni Strazzabosco1,#
1 Department of Environmental and Prevention Sciences, University of Ferrara, Ferrara, Italy
2 Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Ferrara, Italy
3 Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy
* Corresponding Author: Daria Bortolotti. Email: email; Giovanna Schiuma. Email: email
# These authors contributed equally to this work

European Cytokine Network https://doi.org/10.32604/ecn.2026.083049

Received 27 March 2026; Accepted 29 May 2026; Published online 24 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 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.

Keywords

Flavivirus; nonstructural protein 1 (NS1); pattern recognition receptor (PRR) signaling modulation; antiviral immunity; inflammation

  • 65

    View

  • 20

    Download

  • 0

    Like

Related articles
Copyright© 2026 Tech Science Press
© 1997-2026 TSP (Henderson, USA) unless otherwise stated

Share Link