Scientific article

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

Published inEMBO Reports, vol. 21, no. 12, e50421
Publication date2020

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.

  • Humans
  • Inflammasomes/genetics
  • Influenza A Virus
  • H3N2 Subtype
  • Influenza A Virus
  • H5N1 Subtype
  • Influenza A virus/genetics
  • Macrophages
  • NIMA-Related Kinases
  • NLR Family
  • Pyrin Domain-Containing 3 Protein/genetics
  • Pyroptosis
Citation (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
Main files (1)
Article (Published version)
ISSN of the journal1469-221X

Technical informations

Creation05/04/2021 1:22:00 PM
First validation05/04/2021 1:22:00 PM
Update time03/16/2023 12:30:58 AM
Status update03/16/2023 12:30:57 AM
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