Soybean-derived Bowman-Birk Inhibitor (BBI) Inhibits HIV Replication in Macrophages.
Soybean-derived Bowman-Birk Inhibitor (BBI) Inhibits HIV Replication in Macrophages.
复制标题
大豆来源的 Bowman-Birk 抑制剂 (BBI) 抑制巨噬细胞中的 HIV 复制。
DOI：
10.1038/srep34752
复制
发表时间：
2016-10-13
影响因子：
4.6
通讯作者：
Ho WZ
中科院分区：
文献类型：
--
作者：
Ma TC;Zhou RH;Wang X;Li JL;Sang M;Zhou L;Zhuang K;Hou W;Guo DY;Ho WZ
鲍曼-伯克抑制剂(Bowman-Birk Inhibitor，BBI)是一种大豆来源的蛋白酶抑制剂，在体外和体内系统中都具有抗炎作用。巨噬细胞在炎症和免疫激活中发挥关键作用，这与HIV疾病的进展有关。在这里，我们研究了BBI对外周血单核细胞来源的巨噬细胞感染HIV的影响。我们证明了BBI可以有效地抑制HIV在巨噬细胞中的复制，而没有细胞毒性。S的研究表明，脑损伤可诱导干扰素-β和多种干扰素刺激基因的表达，包括粘病毒耐药蛋白2(MX2)、2‘，5’-寡腺苷合成酶(OAS-1)、病毒抑制蛋白(蛇毒)、ISG15和ISG56。巨噬细胞的BBI治疗也增加了几个已知的HIV限制因子的表达，包括APOBEC3F、APOBEC3G和Tetherin。此外，BBI还促进了干扰素-β的关键调节因子irf3的磷酸化。I型干扰素受体中和抗体对β途径的抑制可阻断BBI介导的抗HIV因子的诱导和对巨噬细胞中HIV的抑制作用。BBI可以激活干扰素-β介导的信号通路，启动巨噬细胞的细胞内天然免疫，并在病毒复制周期的多个步骤有效地抑制HIV，这些发现表明BBI作为一种替代的、经济有效的抗HIV天然产物有必要进一步研究。
The Bowman-Birk inhibitor (BBI), a soybean-derived protease inhibitor, is known to have anti-inflammatory effect in both in vitro and in vivo systems. Macrophages play a key role in inflammation and immune activation, which is implicated in HIV disease progression. Here, we investigated the effect of BBI on HIV infection of peripheral blood monocyte-derived macrophages. We demonstrated that BBI could potently inhibit HIV replication in macrophages without cytotoxicity. Investigation of the mechanism(s) of BBI action on HIV showed that BBI induced the expression of IFN-β and multiple IFN stimulated genes (ISGs), including Myxovirus resistance protein 2 (Mx2), 2′,5′-oligoadenylate synthetase (OAS-1), Virus inhibitory protein (viperin), ISG15 and ISG56. BBI treatment of macrophages also increased the expression of several known HIV restriction factors, including APOBEC3F, APOBEC3G and tetherin. Furthermore, BBI enhanced the phosphorylation of IRF3, a key regulator of IFN-β. The inhibition of IFN-β pathway by the neutralization antibody to type I IFN receptor (Anti-IFNAR) abolished BBI-mediated induction of the anti-HIV factors and inhibition of HIV in macrophages. These findings that BBI could activate IFN-β-mediated signaling pathway, initialize the intracellular innate immunity in macrophages and potently inhibit HIV at multiple steps of viral replication cycle indicate the necessity to further investigate BBI as an alternative and cost-effective anti-HIV natural product.
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