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Influenza A Virus NS1 Protein Inhibits the NLRP3 Inflammasome
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 form...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433236/ https://www.ncbi.nlm.nih.gov/pubmed/25978411 http://dx.doi.org/10.1371/journal.pone.0126456 |
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author | Cheong, Woo-Chang Kang, Hye-Ri Yoon, Hyunyee Kang, Suk-Jo Ting, Jenny P.-Y. Song, Moon Jung |
author_facet | Cheong, Woo-Chang Kang, Hye-Ri Yoon, Hyunyee Kang, Suk-Jo Ting, Jenny P.-Y. Song, Moon Jung |
author_sort | Cheong, Woo-Chang |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4433236 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44332362015-05-27 Influenza A Virus NS1 Protein Inhibits the NLRP3 Inflammasome Cheong, Woo-Chang Kang, Hye-Ri Yoon, Hyunyee Kang, Suk-Jo Ting, Jenny P.-Y. Song, Moon Jung PLoS One Research Article 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. Public Library of Science 2015-05-15 /pmc/articles/PMC4433236/ /pubmed/25978411 http://dx.doi.org/10.1371/journal.pone.0126456 Text en © 2015 Cheong et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Cheong, Woo-Chang Kang, Hye-Ri Yoon, Hyunyee Kang, Suk-Jo Ting, Jenny P.-Y. Song, Moon Jung Influenza A Virus NS1 Protein Inhibits the NLRP3 Inflammasome |
title | Influenza A Virus NS1 Protein Inhibits the NLRP3 Inflammasome |
title_full | Influenza A Virus NS1 Protein Inhibits the NLRP3 Inflammasome |
title_fullStr | Influenza A Virus NS1 Protein Inhibits the NLRP3 Inflammasome |
title_full_unstemmed | Influenza A Virus NS1 Protein Inhibits the NLRP3 Inflammasome |
title_short | Influenza A Virus NS1 Protein Inhibits the NLRP3 Inflammasome |
title_sort | influenza a virus ns1 protein inhibits the nlrp3 inflammasome |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433236/ https://www.ncbi.nlm.nih.gov/pubmed/25978411 http://dx.doi.org/10.1371/journal.pone.0126456 |
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