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Vous êtes ici : Accueil / Équipes / Horvat B - IbIV / Actualités / Nipah virus W protein harnesses nuclear 14-3-3 to inhibit NF-κB-induced proinflammatory response

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

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.

Enchéry F, Dumont C, Iampietro M, Pelissier R, Aurine N, Bloyet LM, Carbonnelle C, Mathieu C, Journo C, Gerlier D, Horvat B.

Commun Biol. 2021 Nov 16;4(1):1292. doi: 10.1038/s42003-021-02797-5.