Institute of Virology, Medical University of Innsbruck, Innsbruck, Austria.
Institute of Hygiene & Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
Front Immunol. 2020 Oct 28;11:569549. doi: 10.3389/fimmu.2020.569549. eCollection 2020.
The complement system has developed different strategies to clear infections by several effector mechanisms, such as opsonization, which supports phagocytosis, attracting immune cells by C3 and C5 cleavage products, or direct killing of pathogens by the formation of the membrane attack complex (MAC). As the Zika virus (ZIKV) activates the classical complement pathway and thus has to avoid clearance by the complement system, we analyzed putative viral escape mechanisms, which limit virolysis. We identified binding of the recombinant viral envelope E protein to components of the terminal pathway complement (C5b6, C7, C8, and C9) by ELISA. Western blot analyses revealed that ZIKV E protein interfered with the polymerization of C9, induced on cellular surfaces, either by purified terminal complement proteins or by normal human serum (NHS) as a source of the complement. Further, the hemolytic activity of NHS was significantly reduced in the presence of the recombinant E protein or entire viral particles. This data indicates that ZIKV reduces MAC formation and complement-mediated lysis by binding terminal complement proteins to the viral E protein.
补体系统通过多种效应机制（如调理作用，支持吞噬作用）来清除感染，通过 C3 和 C5 裂解产物吸引免疫细胞，或者通过形成膜攻击复合物 (MAC) 直接杀死病原体。由于寨卡病毒 (ZIKV) 激活经典补体途径，因此必须避免被补体系统清除，我们分析了可能的病毒逃逸机制，这些机制限制了病毒裂解。我们通过 ELISA 鉴定了重组病毒包膜 E 蛋白与末端补体途径成分（C5b6、C7、C8 和 C9）的结合。Western blot 分析表明，ZIKV E 蛋白干扰 C9 在细胞表面的聚合，这种聚合可以由纯化的末端补体蛋白诱导，也可以由正常人血清（NHS）作为补体的来源诱导。此外，在存在重组 E 蛋白或整个病毒颗粒的情况下，NHS 的溶血活性显著降低。这些数据表明，ZIKV 通过将末端补体蛋白结合到病毒 E 蛋白上来减少 MAC 的形成和补体介导的裂解。
