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 - Apr 1 2016

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

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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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, M, Chen, IY, Kawaguchi, A, Koshiba, T, Nagata, K, Takeyama, H, Hasegawa, H & Ichinohe, T 2016, 'The RNA- and TRIM25-binding domains of influenza virus NS1 protein are essential for suppression of NLRP3 inflammasomemediated interleukin-1β secretion', Journal of virology, vol. 90, no. 8, pp. 4105-4114. https://doi.org/10.1128/JVI.00120-16
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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