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 5000kDa) 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 (2000kDa) 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.
| Original language | English |
|---|---|
| Pages (from-to) | 9700-9708 |
| Number of pages | 9 |
| Journal | Biomaterials |
| Volume | 34 |
| Issue number | 37 |
| DOIs | |
| Publication status | Published - 2013 Dec 1 |
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All Science Journal Classification (ASJC) codes
- Bioengineering
- Ceramics and Composites
- Biophysics
- Biomaterials
- Mechanics of Materials
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The antiviral activity of poly-γ-glutamic acid, a polypeptide secreted by Bacillus sp., through induction of CD14-dependent type I interferon responses. / Lee, Wooseong; Lee, Seung Hoon; Ahn, Dae Gyun; Cho, Hee; Sung, Moon Hee; Han, Seung Hyun; Oh, Jong-Won.
In: Biomaterials, Vol. 34, No. 37, 01.12.2013, p. 9700-9708.Research output: Contribution to journal › Article
TY - JOUR
T1 - The antiviral activity of poly-γ-glutamic acid, a polypeptide secreted by Bacillus sp., through induction of CD14-dependent type I interferon responses
AU - Lee, Wooseong
AU - Lee, Seung Hoon
AU - Ahn, Dae Gyun
AU - Cho, Hee
AU - Sung, Moon Hee
AU - Han, Seung Hyun
AU - Oh, Jong-Won
PY - 2013/12/1
Y1 - 2013/12/1
N2 - 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 5000kDa) 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 (2000kDa) 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.
AB - 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 5000kDa) 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 (2000kDa) 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.
UR - http://www.scopus.com/inward/record.url?scp=84884818979&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884818979&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2013.08.067
DO - 10.1016/j.biomaterials.2013.08.067
M3 - Article
C2 - 24016850
AN - SCOPUS:84884818979
VL - 34
SP - 9700
EP - 9708
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
IS - 37
ER -