The antiviral activity of poly-γ-glutamic acid, a polypeptide secreted by Bacillus sp., through induction of CD14-dependent type I interferon responses.
Identifieur interne : 001840 ( Main/Curation ); précédent : 001839; suivant : 001841The antiviral activity of poly-γ-glutamic acid, a polypeptide secreted by Bacillus sp., through induction of CD14-dependent type I interferon responses.
Auteurs : Wooseong Lee [Corée du Sud] ; Seung-Hoon Lee ; Dae-Gyun Ahn ; Hee Cho ; Moon-Hee Sung ; Seung Hyun Han ; Jong-Won OhSource :
- Biomaterials [ 1878-5905 ] ; 2013.
Descripteurs français
- KwdFr :
- Acide polyglutamique (analogues et dérivés), Acide polyglutamique (métabolisme), Acide polyglutamique (usage thérapeutique), Animaux, Antiviraux (métabolisme), Antiviraux (usage thérapeutique), Bacillus (métabolisme), Cellules HEK293, Hepacivirus (), Humains, Hépatite C (traitement médicamenteux), Interféron de type I (immunologie), Lignée cellulaire, Récepteur de type Toll-4 (immunologie), Souris, Syndrome respiratoire aigu sévère (traitement médicamenteux), Virus du SRAS ().
- MESH :
- analogues et dérivés : Acide polyglutamique.
- immunologie : Interféron de type I, Récepteur de type Toll-4.
- métabolisme : Acide polyglutamique, Antiviraux, Bacillus.
- traitement médicamenteux : Hépatite C, Syndrome respiratoire aigu sévère.
- usage thérapeutique : Acide polyglutamique, Antiviraux.
- Animaux, Cellules HEK293, Hepacivirus, Humains, Lignée cellulaire, Souris, Virus du SRAS.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (metabolism), Antiviral Agents (therapeutic use), Bacillus (metabolism), Cell Line, HEK293 Cells, Hepacivirus (drug effects), Hepatitis C (drug therapy), Humans, Interferon Type I (immunology), Lipopolysaccharide Receptors (immunology), Mice, Polyglutamic Acid (analogs & derivatives), Polyglutamic Acid (metabolism), Polyglutamic Acid (therapeutic use), SARS Virus (drug effects), Severe Acute Respiratory Syndrome (drug therapy), Toll-Like Receptor 4 (immunology).
- MESH :
- chemical , analogs & derivatives : Polyglutamic Acid.
- chemical , immunology : Interferon Type I, Lipopolysaccharide Receptors, Toll-Like Receptor 4.
- chemical , metabolism : Antiviral Agents, Polyglutamic Acid.
- chemical , therapeutic use : Antiviral Agents, Polyglutamic Acid.
- drug effects : Hepacivirus, SARS Virus.
- drug therapy : Hepatitis C, Severe Acute Respiratory Syndrome.
- metabolism : Bacillus.
- Animals, Cell Line, HEK293 Cells, Humans, Mice.
Abstract
Poly-γ-glutamic acid (γ-PGA) is an anionic polypeptide secreted by Bacillus sp. that has been shown to activate immune cells through interactions with toll-like receptor 4 (TLR4). However, its ability to induce the type I interferon (IFN) response has not yet been characterized. Here, we demonstrate that γ-PGA induces type I IFN signaling pathway via the TLR4 signaling pathway. The induction required both myeloid differentiation factor 2 (MD2) and the pattern-recognition receptor CD14, which are two TLR4-associated accessory proteins. The γ-PGA with high molecular weights (2000 and 5000 kDa) was able to activate the subsequent signals through TLR4/MD2 to result in dimerization of IRF-3, a transcription factor required for IFN gene expression, leading to increases in mRNA levels of the type I IFN-response genes, 2'-5' OAS and ISG56. Moreover, γ-PGA (2000 kDa) displayed an antiviral activity against SARS coronavirus and hepatitis C virus. Our results identify high-molecular weight γ-PGA as a TLR4 ligand and demonstrate that γ-PGA requires both CD14 and MD2 for the activation of type I IFN responses. Our results suggest that the microbial biopolymer γ-PGA may have therapeutic potential against a broad range of viruses sensitive to type I IFNs.
DOI: 10.1016/j.biomaterials.2013.08.067
PubMed: 24016850
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pubmed:24016850Le document en format XML
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<term>Cell Line</term>
<term>HEK293 Cells</term>
<term>Hepacivirus (drug effects)</term>
<term>Hepatitis C (drug therapy)</term>
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<term>Acide polyglutamique (usage thérapeutique)</term>
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<term>Souris</term>
<term>Syndrome respiratoire aigu sévère (traitement médicamenteux)</term>
<term>Virus du SRAS ()</term>
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<term>Lipopolysaccharide Receptors</term>
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<front><div type="abstract" xml:lang="en">Poly-γ-glutamic acid (γ-PGA) is an anionic polypeptide secreted by Bacillus sp. that has been shown to activate immune cells through interactions with toll-like receptor 4 (TLR4). However, its ability to induce the type I interferon (IFN) response has not yet been characterized. Here, we demonstrate that γ-PGA induces type I IFN signaling pathway via the TLR4 signaling pathway. The induction required both myeloid differentiation factor 2 (MD2) and the pattern-recognition receptor CD14, which are two TLR4-associated accessory proteins. The γ-PGA with high molecular weights (2000 and 5000 kDa) was able to activate the subsequent signals through TLR4/MD2 to result in dimerization of IRF-3, a transcription factor required for IFN gene expression, leading to increases in mRNA levels of the type I IFN-response genes, 2'-5' OAS and ISG56. Moreover, γ-PGA (2000 kDa) displayed an antiviral activity against SARS coronavirus and hepatitis C virus. Our results identify high-molecular weight γ-PGA as a TLR4 ligand and demonstrate that γ-PGA requires both CD14 and MD2 for the activation of type I IFN responses. Our results suggest that the microbial biopolymer γ-PGA may have therapeutic potential against a broad range of viruses sensitive to type I IFNs.</div>
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