tetano
Editor, Senior Moderator
PLoS One. 2015 May 15;10(5):e0126456. doi: 10.1371/journal.pone.0126456.
[h=1]Influenza A Virus NS1 Protein Inhibits the NLRP3 Inflammasome.[/h] Cheong WC[SUP]1[/SUP], Kang HR[SUP]1[/SUP], Yoon H[SUP]2[/SUP], Kang SJ[SUP]3[/SUP], Ting JP[SUP]4[/SUP], Song MJ[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
PMID: 25978411 [PubMed - as supplied by publisher]
[h=1]Influenza A Virus NS1 Protein Inhibits the NLRP3 Inflammasome.[/h] Cheong WC[SUP]1[/SUP], Kang HR[SUP]1[/SUP], Yoon H[SUP]2[/SUP], Kang SJ[SUP]3[/SUP], Ting JP[SUP]4[/SUP], Song MJ[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
PMID: 25978411 [PubMed - as supplied by publisher]