PB1-F2 derived from avian influenza a virus H7N9 induces inflammation via activation of the NLRP3 inflammasome

Pinar, Anita, Dowling, Jennifer K., Bitto, Natalie J., Robertson, Avril B., Latz, Eicke, Stewart, Cameron R., Drummond, Grant R., Cooper, Matthew A., McAuley, Julie L., Tate, Michelle D. and Mansell, Ashley (2017) PB1-F2 derived from avian influenza a virus H7N9 induces inflammation via activation of the NLRP3 inflammasome. The Journal of Biological Chemistry, 292 3: 826-836. doi:10.1074/jbc.M116.756379

Author Pinar, Anita
Dowling, Jennifer K.
Bitto, Natalie J.
Robertson, Avril B.
Latz, Eicke
Stewart, Cameron R.
Drummond, Grant R.
Cooper, Matthew A.
McAuley, Julie L.
Tate, Michelle D.
Mansell, Ashley
Title PB1-F2 derived from avian influenza a virus H7N9 induces inflammation via activation of the NLRP3 inflammasome
Journal name The Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2017-01-20
Year available 2016
Sub-type Article (original research)
DOI 10.1074/jbc.M116.756379
Open Access Status Not yet assessed
Volume 292
Issue 3
Start page 826
End page 836
Total pages 11
Place of publication Bethesda, MD United States
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Subject 1303 Biochemistry
1312 Molecular Biology
1307 Cell Biology
Abstract The emergence of avian H7N9 influenza A virus (IAV) in humans with associated high mortality, has highlighted the threat of a potential pandemic. Fatal H7N9 infections are characterised by hyperinflammation and increased cellular infiltrates in the lung. Currently there are limited therapies to address the pathologies associated with H7N9 infection and what virulence factors may contribute to these pathologies. We have found that PB1-F2 derived from H7N9 activates the NLRP3 inflammasome and induces lung inflammation and cellular recruitment that is NLRP3 dependent. We have also shown that H7N9 and A/Puerto Rico/H1N1 (PR8)PB1-F2 peptide treatment induces significant mitochondrial reactive oxygen production which contributes to NLRP3 activation. Importantly, treatment of cells or mice with the specific NLRP3 inhibitor MCC950 significantly reduces IL-1β maturation and lung cellular recruitment and cytokine production. Together, these results suggest that PB1-F2 from H7N9 avian IAV may be a major contributory factor to disease pathophysiology and excessive inflammation characteristic of clinical infections and that targeting the NLRP3 inflammasome may be an effective means to reduce the inflammatory burden associated with H7N9 infections.
Keyword Inflammasome
Interleukin 1 (IL-1)
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 8 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 8 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Thu, 05 Jan 2017, 01:33:06 EST by Susan Allen on behalf of Institute for Molecular Bioscience