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Title

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

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Published in EMBO Reports. 2020, vol. 21, no. 12, p. e50421
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.
Keywords HumansInflammasomes/geneticsInfluenza A VirusH3N2 SubtypeInfluenza A VirusH5N1 SubtypeInfluenza A virus/geneticsMacrophagesNIMA-Related KinasesNLR FamilyPyrin Domain-Containing 3 Protein/geneticsPyroptosis
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PMID: 33180976
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Article (Published version) (1.9 MB) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research groups Modulation de la flore microbienne dans des hôtes infectés par un virus (947)
Pathologie et immunologie (906)
Projects FNS: 310030_155949; 310030_155949/2; 310030_182475/1
FNS: 310030-185255
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(ISO format)
BOAL P. T. DE CARVALHO, Inès et al. Influenza A viruses limit NLRP3-NEK7-complex formation and pyroptosis in human macrophages. In: EMBO Reports, 2020, vol. 21, n° 12, p. e50421. doi: 10.15252/embr.202050421 https://archive-ouverte.unige.ch/unige:151430

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Deposited on : 2021-05-05

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