The antiviral activity of poly-¦Ã-glutamic acid, a polypeptide secreted by Bacillus sp., through induction of CD14-dependent type I interferon responses

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• 作者：Wooseong Lee ; Seung-Hoon Lee ; Dae-Gyun Ahn ; Hee Cho ; Moon-Hee Sung ; Seung Hyun Han ; Jong-Won Oh
• 关键词：Poly-¦Ã-glutamic acid ; Interferon ; TLR4 ; SARS coronavirus ; Hepatitis C virus ; Antiviral agent
• 刊名：Biomaterials
• 出版年：2013
• 出版时间：December, 2013
• 年：2013
• 卷：34
• 期：37
• 页码：9700-9708
• 全文大小：1899 K

文摘

Poly-¦Ã-glutamic acid (¦Ã-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 ¦Ã-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 ¦Ã-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¡ä¨C5¡ä OAS and ISG56. Moreover, ¦Ã-PGA (2000?kDa) displayed an antiviral activity against SARS coronavirus and hepatitis C virus. Our results identify high-molecular weight ¦Ã-PGA as a TLR4 ligand and demonstrate that ¦Ã-PGA requires both CD14 and MD2 for the activation of type I IFN responses. Our results suggest that the microbial biopolymer ¦Ã-PGA may have therapeutic potential against a broad range of viruses sensitive to type I IFNs.