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Nipah virus W protein harnesses nuclear 14-3-3 to inhibit NF-κB-induced proinflammatory response

Abstract : Abstract Nipah virus (NiV) is a highly pathogenic emerging bat-borne Henipavirus that has caused numerous outbreaks with public health concerns. It is able to inhibit the host innate immune response. Since the NF-κB pathway plays a crucial role in the innate antiviral response as a major transcriptional regulator of inflammation, we postulated its implication in the still poorly understood NiV immunopathogenesis. We report here that NiV inhibits the canonical NF-κB pathway via its nonstructural W protein. Translocation of the W protein into the nucleus causes nuclear accumulation of the cellular scaffold protein 14-3-3 in both African green monkey and human cells infected by NiV. Excess of 14-3-3 in the nucleus was associated with a reduction of NF-κB p65 subunit phosphorylation and of its nuclear accumulation. Importantly, W-S449A substitution impairs the binding of the W protein to 14-3-3 and the subsequent suppression of NF-κB signaling, thus restoring the production of proinflammatory cytokines. Our data suggest that the W protein increases the steady-state level of 14-3-3 in the nucleus and consequently enhances 14-3-3-mediated negative feedback on the NF-κB pathway. These findings provide a mechanistic model of W-mediated disruption of the host inflammatory response, which could contribute to the high severity of NiV infection.
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Contributor : Cyrille Mathieu Connect in order to contact the contributor
Submitted on : Wednesday, September 14, 2022 - 12:01:04 PM
Last modification on : Saturday, September 24, 2022 - 3:10:05 PM




François Enchéry, Claire Dumont, Mathieu Iampietro, Rodolphe Pelissier, Noémie Aurine, et al.. Nipah virus W protein harnesses nuclear 14-3-3 to inhibit NF-κB-induced proinflammatory response. Communications Biology, Nature Publishing Group, 2021, 4 (1), pp.1292. ⟨10.1038/s42003-021-02797-5⟩. ⟨hal-03777061⟩



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