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• W4387327977 endingPage "130483" @default.
• W4387327977 startingPage "130483" @default.
• W4387327977 abstract "During viral infections, nucleic acid sensing by intracellular receptors can trigger type I interferon (IFN-I) production, key mediators in antiviral innate immunity. However, many flaviviruses use non-structural proteins to evade immune sensing favoring their survival. These mechanisms remain poorly characterized. Here, we studied the role of Zika virus (ZIKV) NS4B protein in the inhibition of IFN-I induction pathway and its biophysical interaction with host proteins.Using different cell-based assays, we studied the effect of ZIKV NS4B in the activation of interferon regulatory factors (IRFs), NF-κB, cytokines secretion and the expression of interferon-stimulating genes (ISG). We also analyzed the in vitro interaction between recombinant ZIKV NS4B and TANK-binding kinase 1 (TBK1) using surface plasmon resonance (SPR).Transfection assays showed that ZIKV NS4B inhibits IRFs activation involved in different nucleic acid sensing cascades. Cells expressing NS4B secreted lower levels of IFN-β and IL-6. Furthermore, early induction of ISGs was also restricted by ZIKV NS4B. For the first time, we demonstrate by SPR assays that TBK1, a critical component in IFN-I production pathway, binds directly to ZIKV NS4B (KD of 3.7 × 10-6 M). In addition, we show that the N-terminal region of NS4B is directly involved in this interaction.Altogether, our results strongly support that ZIKV NS4B affects nucleic acid sensing cascades and disrupts the TBK1/IRF3 axis, leading to an impairment of IFN-β production.This study provides the first biophysical data of the interaction between ZIKV NS4B and TBK1, and highlights the role of ZIKV NS4B in evading the early innate immune response." @default.
• W4387327977 created "2023-10-05" @default.
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• W4387327977 date "2023-12-01" @default.
• W4387327977 modified "2023-10-15" @default.
• W4387327977 title "Zika virus NS4B protein targets TANK-binding kinase 1 and inhibits type I interferon production" @default.
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• W4387327977 doi "https://doi.org/10.1016/j.bbagen.2023.130483" @default.
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