The RNA- and TRIM25-binding domains of influenza virus NS1 protein are essential for suppression of NLRP3 inflammasomemediated interleukin-1β secretion

Miyu Moriyama, I. Yin Chen, Atsushi Kawaguchi, Takumi Koshiba, Kyosuke Nagata, Haruko Takeyama, Hideki Hasegawa, Takeshi Ichinohe

    Research output: Contribution to journalArticle

    33 Citations (Scopus)

    Abstract

    Inflammasomes are cytosolic multimolecular protein complexes that stimulate the activation of caspase-1 and the release of mature forms of interleukin-1β (IL-1β) and IL-18. We previously demonstrated that the influenza A virus M2 protein stimulates IL-1β secretion following activation of the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain- containing 3 (NLRP3) inflammasome. The nonstructural protein 1 (NS1) of influenza virus inhibits caspase-1 activation and IL-1β secretion. However, the precise mechanism by which NS1 inhibits IL-1β secretion remains unknown. Here, we showed that J774A.1 macrophages stably expressing the NS1 protein inhibited IL-1β secretion after infection with recombinant influenza virus lacking the NS1 gene. Coimmunoprecipitation assay revealed that the NS1 protein interacts with NLRP3. Importantly, the NS1 protein inhibited the NLRP3/ASC-induced single-speck formation required for full activation of inflammasomes. The NS1 protein of other influenza virus strains, including a recent pandemic strain, also inhibited inflammasome-mediated IL-1β secretion. The NS1 RNA-binding domain (basic residues 38 and 41) and TRIM25-binding domain (acidic residues 96 and 97) were required for suppression of NLRP3 inflammasome-mediated IL-1β secretion. These results shed light on a mechanism by which the NS1 protein of influenza virus suppresses NLRP3 inflammasome-mediated IL-1β secretion.

    Original languageEnglish
    Pages (from-to)4105-4114
    Number of pages10
    JournalJournal of Virology
    Volume90
    Issue number8
    DOIs
    Publication statusPublished - 2016 Apr 1

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    interleukin-1
    Orthomyxoviridae
    Interleukin-1
    secretion
    RNA
    receptors
    Inflammasomes
    Proteins
    proteins
    Caspase 1
    caspase-1
    NLR Proteins
    Pyrin Domain
    RNA-Binding Motifs
    Interleukin-18
    interleukin-18
    Pandemics
    pandemic
    Influenza A virus
    Nucleotides

    ASJC Scopus subject areas

    • Immunology
    • Virology

    Cite this

    The RNA- and TRIM25-binding domains of influenza virus NS1 protein are essential for suppression of NLRP3 inflammasomemediated interleukin-1β secretion. / Moriyama, Miyu; Chen, I. Yin; Kawaguchi, Atsushi; Koshiba, Takumi; Nagata, Kyosuke; Takeyama, Haruko; Hasegawa, Hideki; Ichinohe, Takeshi.

    In: Journal of Virology, Vol. 90, No. 8, 01.04.2016, p. 4105-4114.

    Research output: Contribution to journalArticle

    Moriyama, Miyu ; Chen, I. Yin ; Kawaguchi, Atsushi ; Koshiba, Takumi ; Nagata, Kyosuke ; Takeyama, Haruko ; Hasegawa, Hideki ; Ichinohe, Takeshi. / The RNA- and TRIM25-binding domains of influenza virus NS1 protein are essential for suppression of NLRP3 inflammasomemediated interleukin-1β secretion. In: Journal of Virology. 2016 ; Vol. 90, No. 8. pp. 4105-4114.
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