Institute of Virology, Medical University of Innsbruck, 6020 Innsbruck, Austria.
Center for Virology, Medical University of Vienna, 1090 Vienna, Austria.
Viruses. 2021 Mar 19;13(3):510. doi: 10.3390/v13030510.
The rapid spread of the virus in Latin America and the association of the infection with microcephaly in newborns or Guillain-Barré Syndrome in adults prompted the WHO to declare the Zika virus (ZIKV) epidemic to be an international public health emergency in 2016. As the virus was first discovered in monkeys and is spread not only by mosquitos but also from human to human, we investigated the stability to the human complement of ZIKV derived from mosquito (ZIKVInsect), monkey (ZIKVVero), or human cells (ZIKVA549 and ZIKVFibro), respectively. At a low serum concentration (10%), which refers to complement concentrations found on mucosal surfaces, the virus was relatively stable at 37 °C. At higher complement levels (up to 50% serum concentration), ZIKV titers differed significantly depending on the cell line used for the propagation of the virus. While the viral titer of ZIKVInsect decreased about two orders in magnitude, when incubated with human serum, the virus derived from human cells was more resistant to complement-mediated lysis (CML). By virus-capture assay and Western blots, the complement regulator protein CD55 was identified to be incorporated into the viral envelope. Blocking of CD55 by neutralizing Abs significantly increased the sensitivity to human complement. Taken together, these data indicate that the incorporation of CD55 from human cells contributes to the stability of ZIKV against complement-mediated virolysis.
病毒在拉丁美洲的迅速传播，以及该感染与新生儿小头畸形或成人吉兰-巴雷综合征的关联，促使世界卫生组织在 2016 年宣布寨卡病毒（ZIKV）疫情为国际公共卫生紧急事件。由于该病毒最初是在猴子身上发现的，不仅通过蚊子传播，还可以在人与人之间传播，因此我们分别研究了来自蚊子（ZIKVInsect）、猴子（ZIKVVero）或人类细胞（ZIKVA549 和 ZIKVFibro）的 ZIKV 对人类补体的稳定性。在低血清浓度（10%）下，这是指在黏膜表面发现的补体浓度，病毒在 37°C 下相对稳定。在更高的补体水平（高达 50%的血清浓度）下，ZIKV 滴度根据用于病毒繁殖的细胞系而有显著差异。当用人类血清孵育时，虽然来自昆虫的 ZIKV 病毒滴度降低了约两个数量级，但来自人类细胞的病毒对补体介导的溶解（CML）更具抵抗力。通过病毒捕获测定和 Western blot，鉴定出补体调节蛋白 CD55 被整合到病毒包膜中。用中和抗体阻断 CD55 可显著增加对人类补体的敏感性。总之，这些数据表明，来自人类细胞的 CD55 的掺入有助于 ZIKV 抵抗补体介导的病毒溶解。
