The Scorpion Venom Peptide Smp76 Inhibits Viral Infection by Regulating Type-I Interferon Response
The Scorpion Venom Peptide Smp76 Inhibits Viral Infection by Regulating Type-I Interferon Response
复制标题
蝎毒肽Smp76通过调节I型干扰素反应抑制病毒感染
DOI：
10.1007/s12250-018-0068-4
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发表时间：
2018-12-01
影响因子：
5.5
通讯作者：
Cao, Zhijian
中科院分区：
文献类型：
--
作者：
Ji, Zhenglin;Li, Fangfang;Cao, Zhijian
登革热病毒(DENV)和寨卡病毒(ZIKV)已经在发展中国家的许多国家蔓延，每年感染数百万人，对人类健康和经济造成严重危害。不幸的是，针对这些病毒的有效疫苗和疗法寥寥无几。因此，发现新的抗病毒药物至关重要。本研究成功地在大肠杆菌BL21(DE3)中表达和纯化了天蝎毒肽(Smp76)。重组Smp76(RSmp76)在培养的细胞系和原代小鼠巨噬细胞中均能有效抑制DENV和ZIKV的感染，并呈剂量依赖关系。有趣的是，rSmp76并不直接灭活病毒颗粒，而是抑制已建立的病毒感染，类似于干扰素(干扰素)的作用。从机制上讲，rSmp76通过激活干扰素调节转录因子3(IRF3)的磷酸化，增强I型干扰素应答，抑制病毒感染，从而上调干扰素-α的表达。这一机制与传统的抗病毒抗菌肽(AMPs)有很大不同。总体而言，蝎毒多肽Smp76是一种潜在的新型抗病毒药物，具有涉及I型干扰素反应的独特机制，表明天然AMP可以通过免疫调节剂的作用增强免疫力。
Dengue virus (DENV) and Zika virus (ZIKV) have spread throughout many countries in the developing world and infect millions of people every year, causing severe harm to human health and the economy. Unfortunately, there are few effective vaccines and therapies available against these viruses. Therefore, the discovery of new antiviral agents is critical. Herein, a scorpion venom peptide (Smp76) characterized from Scorpio maurus palmatus was successfully expressed and purified in Escherichia coli BL21(DE3). The recombinant Smp76 (rSmp76) was found to effectively inhibit DENV and ZIKV infections in a dose-dependent manner in both cultured cell lines and primary mouse macrophages. Interestingly, rSmp76 did not inactivate the viral particles directly but suppressed the established viral infection, similar to the effect of interferon (IFN)-. Mechanistically, rSmp76 was revealed to upregulate the expression of IFN- by activating interferon regulatory transcription factor 3 (IRF3) phosphorylation, enhancing the type-I IFN response and inhibiting viral infection. This mechanism is significantly different from traditional virucidal antimicrobial peptides (AMPs). Overall, the scorpion venom peptide Smp76 is a potential new antiviral agent with a unique mechanism involving type-I IFN responses, demonstrating that natural AMPs can enhance immunity by functioning as immunomodulators.