tetano
Editor, Senior Moderator
Front Microbiol
. 2021 Nov 12;12:778950.
doi: 10.3389/fmicb.2021.778950. eCollection 2021.
NLRP3 Inflammasome Activation Enhanced by TRIM25 is Targeted by the NS1 Protein of 2009 Pandemic Influenza A Virus
Hong-Su Park[SUP] 1 [/SUP], Yao Lu[SUP] 1 [/SUP], Kannupriya Pandey[SUP] 1 2 [/SUP], GuanQun Liu[SUP] 1 [/SUP], Yan Zhou[SUP] 1 2 [/SUP]
Affiliations
Abstract
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.
Keywords: NLRP3 inflammasome; NS1; TRIM25; caspase-1; influenza A virus; interleukin-1 beta; tripartite motif-containing protein.
. 2021 Nov 12;12:778950.
doi: 10.3389/fmicb.2021.778950. eCollection 2021.
NLRP3 Inflammasome Activation Enhanced by TRIM25 is Targeted by the NS1 Protein of 2009 Pandemic Influenza A Virus
Hong-Su Park[SUP] 1 [/SUP], Yao Lu[SUP] 1 [/SUP], Kannupriya Pandey[SUP] 1 2 [/SUP], GuanQun Liu[SUP] 1 [/SUP], Yan Zhou[SUP] 1 2 [/SUP]
Affiliations
- PMID: 34867921
- PMCID: PMC8633893
- DOI: 10.3389/fmicb.2021.778950
Abstract
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.
Keywords: NLRP3 inflammasome; NS1; TRIM25; caspase-1; influenza A virus; interleukin-1 beta; tripartite motif-containing protein.