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Influenza A viruses limit NLRP3-NEK7-complex formation and pyroptosis in human macrophages

Boal-Carvalho I, Mazel-Sanchez B, Silva F, Garnier L, Yildiz S, Bonifacio JPPL, Niu C, Williams N, Francois P, Schwerk N, Schoning J, Carlens J, Viemann D, Hugues S, Schmolke M (2020)

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Publication Type: Journal article

Publication year: 2020

Journal

Book Volume: 21

Article Number: e50421

Journal Issue: 12

DOI: 10.15252/embr.202050421

Abstract

Pyroptosis is a fulminant form of macrophage cell death, contributing to release of pro-inflammatory cytokines. In humans, it depends on caspase 1/4-activation of gasdermin D and is characterized by the release of cytoplasmic content. Pathogens apply strategies to avoid or antagonize this host response. We demonstrate here that a small accessory protein (PB1-F2) of contemporary H5N1 and H3N2 influenza A viruses (IAV) curtails fulminant cell death of infected human macrophages. Infection of macrophages with a PB1-F2-deficient mutant of a contemporary IAV resulted in higher levels of caspase-1 activation, cleavage of gasdermin D, and release of LDH and IL-1β. Mechanistically, PB1-F2 limits transition of NLRP3 from its auto-repressed and closed confirmation into its active state. Consequently, interaction of a recently identified licensing kinase NEK7 with NLRP3 is diminished, which is required to initiate inflammasome assembly.

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How to cite

APA:

Boal-Carvalho, I., Mazel-Sanchez, B., Silva, F., Garnier, L., Yildiz, S., Bonifacio, J.P.P.L.,... Schmolke, M. (2020). Influenza A viruses limit NLRP3-NEK7-complex formation and pyroptosis in human macrophages. EMBO Reports, 21(12). https://doi.org/10.15252/embr.202050421

MLA:

Boal-Carvalho, Ines, et al. "Influenza A viruses limit NLRP3-NEK7-complex formation and pyroptosis in human macrophages." EMBO Reports 21.12 (2020).

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