NLRP3 Inflammasome Activation Enhanced by TRIM25 is Targeted by the NS1 Protein of 2009 Pandemic Influenza A Virus
Nucleotide-binding domain and leucine-rich repeat-containing protein 3 (NLRP3) inflammasome-mediated interleukin-1 beta (IL-1β) production is one of the crucial responses in innate immunity upon infection with viruses including influenza A virus (IAV) and is modulated by both viral and host cellular...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:becdf8cc9f8146a6ba04e53c2a457f122021-11-12T13:55:23ZNLRP3 Inflammasome Activation Enhanced by TRIM25 is Targeted by the NS1 Protein of 2009 Pandemic Influenza A Virus1664-302X10.3389/fmicb.2021.778950https://doaj.org/article/becdf8cc9f8146a6ba04e53c2a457f122021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.778950/fullhttps://doaj.org/toc/1664-302XNucleotide-binding domain and leucine-rich repeat-containing protein 3 (NLRP3) inflammasome-mediated interleukin-1 beta (IL-1β) production is one of the crucial responses in innate immunity upon infection with viruses including influenza A virus (IAV) and is modulated by both viral and host cellular proteins. Among host proteins involved, we identified tripartite motif-containing protein 25 (TRIM25) as a positive regulator of porcine NLRP3 inflammasome-mediated IL-1β production. TRIM25 achieved this function by enhancing the pro-caspase-1 interaction with apoptosis-associated speck-like protein containing caspase recruitment domain (ASC). The N-terminal RING domain, particularly residues predicted to be critical for the E3 ligase activity of TRIM25, was responsible for this enhancement. However, non-structural protein 1 (NS1) C-terminus of 2009 pandemic IAV interfered with this action by interacting with TRIM25, leading to diminished association between pro-caspase-1 and ASC. These findings demonstrate that TRIM25 promotes the IL-1β signaling, while it is repressed by IAV NS1 protein, revealing additional antagonism of the NS1 against host pro-inflammatory responses.Hong-Su ParkYao LuKannupriya PandeyKannupriya PandeyGuanQun LiuYan ZhouYan ZhouFrontiers Media S.A.articleNLRP3 inflammasomeinterleukin-1 betacaspase-1tripartite motif-containing proteinTRIM25influenza A virusMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021) |
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NLRP3 inflammasome interleukin-1 beta caspase-1 tripartite motif-containing protein TRIM25 influenza A virus Microbiology QR1-502 |
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NLRP3 inflammasome interleukin-1 beta caspase-1 tripartite motif-containing protein TRIM25 influenza A virus Microbiology QR1-502 Hong-Su Park Yao Lu Kannupriya Pandey Kannupriya Pandey GuanQun Liu Yan Zhou Yan Zhou NLRP3 Inflammasome Activation Enhanced by TRIM25 is Targeted by the NS1 Protein of 2009 Pandemic Influenza A Virus |
description |
Nucleotide-binding domain and leucine-rich repeat-containing protein 3 (NLRP3) inflammasome-mediated interleukin-1 beta (IL-1β) production is one of the crucial responses in innate immunity upon infection with viruses including influenza A virus (IAV) and is modulated by both viral and host cellular proteins. Among host proteins involved, we identified tripartite motif-containing protein 25 (TRIM25) as a positive regulator of porcine NLRP3 inflammasome-mediated IL-1β production. TRIM25 achieved this function by enhancing the pro-caspase-1 interaction with apoptosis-associated speck-like protein containing caspase recruitment domain (ASC). The N-terminal RING domain, particularly residues predicted to be critical for the E3 ligase activity of TRIM25, was responsible for this enhancement. However, non-structural protein 1 (NS1) C-terminus of 2009 pandemic IAV interfered with this action by interacting with TRIM25, leading to diminished association between pro-caspase-1 and ASC. These findings demonstrate that TRIM25 promotes the IL-1β signaling, while it is repressed by IAV NS1 protein, revealing additional antagonism of the NS1 against host pro-inflammatory responses. |
format |
article |
author |
Hong-Su Park Yao Lu Kannupriya Pandey Kannupriya Pandey GuanQun Liu Yan Zhou Yan Zhou |
author_facet |
Hong-Su Park Yao Lu Kannupriya Pandey Kannupriya Pandey GuanQun Liu Yan Zhou Yan Zhou |
author_sort |
Hong-Su Park |
title |
NLRP3 Inflammasome Activation Enhanced by TRIM25 is Targeted by the NS1 Protein of 2009 Pandemic Influenza A Virus |
title_short |
NLRP3 Inflammasome Activation Enhanced by TRIM25 is Targeted by the NS1 Protein of 2009 Pandemic Influenza A Virus |
title_full |
NLRP3 Inflammasome Activation Enhanced by TRIM25 is Targeted by the NS1 Protein of 2009 Pandemic Influenza A Virus |
title_fullStr |
NLRP3 Inflammasome Activation Enhanced by TRIM25 is Targeted by the NS1 Protein of 2009 Pandemic Influenza A Virus |
title_full_unstemmed |
NLRP3 Inflammasome Activation Enhanced by TRIM25 is Targeted by the NS1 Protein of 2009 Pandemic Influenza A Virus |
title_sort |
nlrp3 inflammasome activation enhanced by trim25 is targeted by the ns1 protein of 2009 pandemic influenza a virus |
publisher |
Frontiers Media S.A. |
publishDate |
2021 |
url |
https://doaj.org/article/becdf8cc9f8146a6ba04e53c2a457f12 |
work_keys_str_mv |
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