Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cell Host Microbe. 2010 Aug 19;8(2):186-95. doi: 10.1016/j.chom.2010.07.007.
An intact complement system is crucial for limiting West Nile virus (WNV) dissemination. Herein, we define how complement directly restricts flavivirus infection in an antibody-independent fashion. Mannose-binding lectin (MBL) recognized N-linked glycans on the structural proteins of WNV and Dengue virus (DENV), resulting in neutralization through a C3- and C4-dependent mechanism that utilized both the canonical and bypass lectin activation pathways. For WNV, neutralization occurred with virus produced in insect cells, whereas for DENV, neutralization of insect and mammalian cell-derived virus was observed. Mechanism of action studies suggested that the MBL-dependent neutralization occurred, in part, by blocking viral fusion. Experiments in mice showed an MBL-dependent accelerated intravascular clearance of DENV or a WNV mutant with two N-linked glycans on its E protein, but not with wild-type WNV. Our studies show that MBL recognizes terminal mannose-containing carbohydrates on flaviviruses, resulting in neutralization and efficient clearance in vivo.
完整的补体系统对于限制西尼罗河病毒（WNV）的传播至关重要。在此，我们定义了补体如何以非抗体依赖的方式直接限制黄病毒感染。甘露糖结合凝集素（MBL）识别 WNV 和登革热病毒（DENV）结构蛋白上的 N 连接聚糖，通过 C3 和 C4 依赖性机制导致中和，该机制利用了经典和旁路凝集素激活途径。对于 WNV，中和作用发生在昆虫细胞中产生的病毒上，而对于 DENV，则观察到对昆虫和哺乳动物细胞来源的病毒的中和作用。作用机制研究表明，MBL 依赖性中和作用部分是通过阻止病毒融合来实现的。在小鼠中的实验表明，MBL 依赖性加速了 DENV 或其 E 蛋白上有两个 N 连接聚糖的 WNV 突变体的血管内清除，但对野生型 WNV 则没有。我们的研究表明，MBL 识别黄病毒上末端含有甘露糖的碳水化合物，导致体内中和和有效清除。
