Influenza A virus NS1 protein inhibits the NLRP3 inflammasome

Woo Chang Cheong, Hye Ri Kang, Hyunyee Yoon, Suk Jo Kang, Jenny P Y Ting, Moon Jung Song

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27 Citations (Scopus)

Abstract

The inflammasome is a molecular platform that stimulates the activation of caspase-1 and the processing of pro-interleukin (IL)-1β and pro-IL-18 for secretion. The NOD-like receptor family, pyrin domain containing 3 (NLRP3) protein is activated by diverse molecules and pathogens, leading to the formation of the NLRP3 inflammasome. Recent studies showed that the NLRP3 inflammasome mediates innate immunity against influenza A virus (IAV) infection. In this study, we investigated the function of the IAV non-structural protein 1 (NS1) in the modulation of NLRP3 inflammasome. We found that NS1 proteins derived from both highly pathogenic and low pathogenic strains efficiently decreased secretion of IL-1β and IL-18 from THP-1 cells treated with LPS and ATP. NS1 overexpression significantly impaired the transcription of proinflammatory cytokines by inhibiting transactivation of the nuclear factor-κB (NF-κB), a major transcription activator. Furthermore, NS1 physically interacted with endogenous NLRP3 and activation of the NLRP3 inflammasome was abrogated in NS1-expressing THP-1 cells. These findings suggest that NS1 downregulates NLRP3 inflammasome activation by targeting NLRP3 as well as NF-κB, leading to a reduction in the levels of inflammatory cytokines as a viral immune evasion strategy.

Original languageEnglish
Article number0126456
JournalPLoS One
Volume10
Issue number5
DOIs
Publication statusPublished - 2015 May 15

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Cheong, W. C., Kang, H. R., Yoon, H., Kang, S. J., Ting, J. P. Y., & Song, M. J. (2015). Influenza A virus NS1 protein inhibits the NLRP3 inflammasome. PLoS One, 10(5), [0126456]. https://doi.org/10.1371/journal.pone.0126456