TY - JOUR TI - Influenza A viruses limit NLRP3-NEK7-complex formation and pyroptosis in human macrophages AU - Boal-Carvalho, Inês AU - Mazel-Sanchez, Béryl AU - Silva, Filo AU - Garnier, Laure AU - Yildiz, Soner AU - Bonifacio, Joao PPL AU - Niu, Chengyue AU - Williams, Nathalia AU - Francois, Patrice AU - Schwerk, Nicolaus AU - Schöning, Jennifer AU - Carlens, Julia AU - Viemann, Dorothee AU - Hugues, Stephanie AU - Schmolke, Mirco T2 - EMBO reports AB - 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-1?. 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. DA - 2020/11/12/ PY - 2020 DO - 10.15252/embr.202050421 DP - embopress.org (Atypon) VL - n/a IS - n/a SP - e50421 J2 - EMBO reports SN - 1469-221X UR - https://www.embopress.org/doi/abs/10.15252/embr.202050421 Y2 - 2020/11/13/22:12:10 KW - NEK7 KW - NLRP3 KW - PB1-F2 KW - influenza A virus KW - pyroptosis ER -