Division of Virology, Medical University of Innsbruck, Innsbruck, Austria.
CNRS, CEA, IBS, University of Grenoble Alpes, Grenoble, France.
Front Immunol. 2018 Oct 17;9:2177. doi: 10.3389/fimmu.2018.02177. eCollection 2018.
Although neglected in the past, the interest on Zika virus (ZIKV) raised dramatically in the last several years. 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 ZIKV epidemic to be an international public health emergency in 2016. As the virus gained only limited attention in the past, investigations on interactions of ZIKV with human complement are limited. This prompted us to investigate the stability of the virus to human complement. At low serum concentrations (10%) which refers to complement concentrations found on mucosal surfaces, the virus was relatively stable at 37°C, while at high complement levels (50% serum concentration) ZIKV titers were dramatically reduced, although the virus remained infectious for about 4-5 min under these conditions. The classical pathway was identified as the main actor of complement activation driven by IgM antibodies. In addition, direct binding of C1q to both envelope and NS1 proteins was observed. Formation of the MAC on the viral surface and thus complement-mediated lysis and not opsonization seems to be essential for the reduction of viral titers.
尽管过去被忽视，但寨卡病毒（ZIKV）的关注度在过去几年中急剧上升。该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 年宣布寨卡病毒疫情为国际公共卫生紧急事件。由于过去该病毒受到的关注有限，对寨卡病毒与人类补体相互作用的研究也很有限。这促使我们研究病毒对人类补体的稳定性。在低血清浓度（10%，指在黏膜表面发现的补体浓度）下，病毒在 37°C 下相对稳定，而在高补体水平（50%血清浓度）下，寨卡病毒滴度显著降低，尽管在这些条件下，病毒仍具有约 4-5 分钟的感染性。经典途径被确定为 IgM 抗体驱动的补体激活的主要作用者。此外，还观察到 C1q 与包膜和 NS1 蛋白的直接结合。在病毒表面形成 MAC，从而介导补体溶解而不是调理作用，似乎对于降低病毒滴度是必要的。
