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Species-specific IL-1β is an inflammatory sensor of Seneca Valley Virus 3C Protease
by
Yuan, Ye
, Zhu, Cheng
, Huang, Xiangyu
, Li, Xin
, Yan, Ya
, Li, Pingwei
, Chai, Lvye
, Jiang, Xiaohan
, Zhao, Zhenchao
, Wang, Haiwei
, Wu, Lei
, Liu, Zheng
, Li, Minjie
in
3C Viral Proteases - metabolism
/ Alveoli
/ Animals
/ Biology and Life Sciences
/ Caspase-1
/ Caspase-4
/ Cell culture
/ Cell death
/ Chromatography
/ Cleavage
/ Cysteine Endopeptidases - metabolism
/ Enzymes
/ Humans
/ Hydrophobicity
/ IL-1β
/ Infections
/ Inflammasomes
/ Inflammasomes - metabolism
/ Inflammation
/ Inflammation - metabolism
/ Interleukin 18
/ Interleukin-1beta - metabolism
/ Macrophages
/ Macrophages, Alveolar - metabolism
/ Macrophages, Alveolar - virology
/ Medicine and Health Sciences
/ Molecular modelling
/ Morphology
/ Mutagenesis
/ Picornaviridae
/ Picornaviridae Infections - metabolism
/ Picornaviridae Infections - virology
/ Plasmids
/ Protease
/ Proteinase
/ Research and Analysis Methods
/ Species Specificity
/ Substrates
/ Swine
/ Viral infections
/ Viral Proteins - metabolism
/ Viruses
2024
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Species-specific IL-1β is an inflammatory sensor of Seneca Valley Virus 3C Protease
by
Yuan, Ye
, Zhu, Cheng
, Huang, Xiangyu
, Li, Xin
, Yan, Ya
, Li, Pingwei
, Chai, Lvye
, Jiang, Xiaohan
, Zhao, Zhenchao
, Wang, Haiwei
, Wu, Lei
, Liu, Zheng
, Li, Minjie
in
3C Viral Proteases - metabolism
/ Alveoli
/ Animals
/ Biology and Life Sciences
/ Caspase-1
/ Caspase-4
/ Cell culture
/ Cell death
/ Chromatography
/ Cleavage
/ Cysteine Endopeptidases - metabolism
/ Enzymes
/ Humans
/ Hydrophobicity
/ IL-1β
/ Infections
/ Inflammasomes
/ Inflammasomes - metabolism
/ Inflammation
/ Inflammation - metabolism
/ Interleukin 18
/ Interleukin-1beta - metabolism
/ Macrophages
/ Macrophages, Alveolar - metabolism
/ Macrophages, Alveolar - virology
/ Medicine and Health Sciences
/ Molecular modelling
/ Morphology
/ Mutagenesis
/ Picornaviridae
/ Picornaviridae Infections - metabolism
/ Picornaviridae Infections - virology
/ Plasmids
/ Protease
/ Proteinase
/ Research and Analysis Methods
/ Species Specificity
/ Substrates
/ Swine
/ Viral infections
/ Viral Proteins - metabolism
/ Viruses
2024
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Species-specific IL-1β is an inflammatory sensor of Seneca Valley Virus 3C Protease
by
Yuan, Ye
, Zhu, Cheng
, Huang, Xiangyu
, Li, Xin
, Yan, Ya
, Li, Pingwei
, Chai, Lvye
, Jiang, Xiaohan
, Zhao, Zhenchao
, Wang, Haiwei
, Wu, Lei
, Liu, Zheng
, Li, Minjie
in
3C Viral Proteases - metabolism
/ Alveoli
/ Animals
/ Biology and Life Sciences
/ Caspase-1
/ Caspase-4
/ Cell culture
/ Cell death
/ Chromatography
/ Cleavage
/ Cysteine Endopeptidases - metabolism
/ Enzymes
/ Humans
/ Hydrophobicity
/ IL-1β
/ Infections
/ Inflammasomes
/ Inflammasomes - metabolism
/ Inflammation
/ Inflammation - metabolism
/ Interleukin 18
/ Interleukin-1beta - metabolism
/ Macrophages
/ Macrophages, Alveolar - metabolism
/ Macrophages, Alveolar - virology
/ Medicine and Health Sciences
/ Molecular modelling
/ Morphology
/ Mutagenesis
/ Picornaviridae
/ Picornaviridae Infections - metabolism
/ Picornaviridae Infections - virology
/ Plasmids
/ Protease
/ Proteinase
/ Research and Analysis Methods
/ Species Specificity
/ Substrates
/ Swine
/ Viral infections
/ Viral Proteins - metabolism
/ Viruses
2024
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Species-specific IL-1β is an inflammatory sensor of Seneca Valley Virus 3C Protease
Journal Article
Species-specific IL-1β is an inflammatory sensor of Seneca Valley Virus 3C Protease
2024
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Overview
Inflammasomes play pivotal roles in inflammation by processing and promoting the secretion of IL-1β. Caspase-1 is involved in the maturation of IL-1β and IL-18, while human caspase-4 specifically processes IL-18. Recent structural studies of caspase-4 bound to Pro-IL-18 reveal the molecular basis of Pro-IL-18 activation by caspase-4. However, the mechanism of caspase-1 processing of pro-IL-1β and other IL-1β-converting enzymes remains elusive. Here, we observed that swine Pro-IL-1β (sPro-IL-1β) exists as an oligomeric precursor unlike monomeric human Pro-IL-1β (hPro-IL-1β). Interestingly, Seneca Valley Virus (SVV) 3C protease cleaves sPro-IL-1β to produce mature IL-1β, while it cleaves hPro-IL-1β but does not produce mature IL-1β in a specific manner. When the inflammasome is blocked, SVV 3C continues to activate IL-1β through direct cleavage in porcine alveolar macrophages (PAMs). Through molecular modeling and mutagenesis studies, we discovered that the pro-domain of sPro-IL-1β serves as an ’exosite’ with its hydrophobic residues docking into a positively charged 3C protease pocket, thereby directing the substrate to the active site. The cleavage of sPro-IL-1β generates a monomeric and active form of IL-1β, initiating the downstream signaling. Thus, these studies provide IL-1β is an inflammatory sensor that directly detects viral protease through an independent pathway operating in parallel with host inflammasomes.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
3C Viral Proteases - metabolism
/ Alveoli
/ Animals
/ Cleavage
/ Cysteine Endopeptidases - metabolism
/ Enzymes
/ Humans
/ IL-1β
/ Interleukin-1beta - metabolism
/ Macrophages, Alveolar - metabolism
/ Macrophages, Alveolar - virology
/ Medicine and Health Sciences
/ Picornaviridae Infections - metabolism
/ Picornaviridae Infections - virology
/ Plasmids
/ Protease
/ Research and Analysis Methods
/ Swine
/ Viruses
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