Mannose-binding lectin binds to Ebola and Marburg envelope glycoproteins, resulting in blocking of virus interaction with DC-SIGN and complement-mediated virus neutralization
Mannose-binding lectin binds to Ebola and Marburg envelope glycoproteins, resulting in blocking of virus interaction with DC-SIGN and complement-mediated virus neutralization
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DOI：
10.1099/vir.0.81199-0
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发表时间：
2005-09-01
影响因子：
3.8
通讯作者：
Spear, GT
中科院分区：
文献类型：
--
作者：
Ji, X;Olinger, GG;Spear, GT
甘露糖结合凝集素(MBL)是一种血清凝集素，介导天然免疫功能，包括激活凝集素补体途径，与一些病毒糖蛋白上表达的碳水化合物结合。在这项研究中，评估了MBL与埃博拉和Marburg包膜糖蛋白假型病毒颗粒的结合能力。与含有水泡性口炎病毒糖蛋白或不含病毒糖蛋白的病毒颗粒相比，含有埃博拉病毒(扎伊尔株)或马尔堡(穆斯克株)包膜糖蛋白的病毒颗粒与固定化MBL的结合水平明显更高。正如以前的研究所观察到的，埃博拉假型病毒与表达凝集素DC-SIGN(树突状细胞特异性细胞间黏附分子3-抓取非整合素)的细胞结合。然而，病毒与MBL预孵育阻断了DC-SIGN介导的与细胞的结合，这表明这两种凝集素结合在埃博拉糖蛋白上的相同或重叠位置。中和实验表明，具有埃博拉或马尔堡(Musoke)糖蛋白假型的病毒可被补体中和，而马尔堡(Ravn株)糖蛋白假型病毒对中和不敏感。中和部分是通过凝集素补体途径，因为缺乏MBL的补体来源在中和带有丝状病毒糖蛋白的假型病毒时效果显著降低；在MBL缺陷的补体中加入纯化的MBL可增加中和作用。这些实验表明，MBL与丝状病毒包膜糖蛋白结合，具有重要的生物学效应，提示MBL在人类感染过程中可以与丝状病毒相互作用。
Mannose-binding lectin (MBL), a serum lectin that mediates innate immune functions including activation of the lectin complement pathway, binds to carbohydrates expressed on some viral glycoproteins. In this study, the ability of MBL to bind to virus particles pseudotyped with Ebola and Marburg envelope glycoproteins was evaluated. Virus particles bearing either Ebola (Zaire strain) or Marburg (Musoke strain) envelope glycoproteins bound at significantly higher levels to immobilized MBL compared with virus particles pseudotyped with vesicular stomatitis virus glycoprotein or with no virus glycoprotein. As observed in previous studies, Ebola-pseudotyped virus bound to cells expressing the lectin DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin). However, pre-incubation of virus with MBL blocked DC-SIGN-mediated binding to cells, suggesting that the two lectins bind at the same or overlapping sites on the Ebola glycoprotein. Neutralization experiments showed that virus pseudotyped with Ebola or Marburg (Musoke) glycoprotein was neutralized by complement, while the Marburg (Ravn strain) glycoprotein-pseudotyped virus was less sensitive to neutralization. Neutralization was partially mediated through the lectin complement pathway, since a complement source deficient in MBL was significantly less effective at neutralizing viruses pseudotyped with filovirus glycoproteins; and addition of purified MBL to the MBL-deficient complement increased neutralization. These experiments demonstrated that MBL binds to filovirus envelope glycoproteins resulting in important biological effects and suggest that MBL can interact with filoviruses during infection in humans.