Department of Biological Sciences, Purdue University, West Lafayette, IN 47907.
Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232.
Proc Natl Acad Sci U S A. 2019 Jan 29;116(5):1591-1596. doi: 10.1073/pnas.1815432116. Epub 2019 Jan 14.
Zika virus (ZIKV) is a major human pathogen and member of the genus in the Flaviviridae family. In contrast to most other insect-transmitted flaviviruses, ZIKV also can be transmitted sexually and from mother to fetus in humans. During recent outbreaks, ZIKV infections have been linked to microcephaly, congenital disease, and Guillain-Barré syndrome. Neutralizing antibodies have potential as therapeutic agents. We report here a 4-Å-resolution cryo-electron microscopy structure of the ZIKV virion in complex with Fab fragments of the potently neutralizing human monoclonal antibody ZIKV-195. The footprint of the ZIKV-195 Fab fragment expands across two adjacent envelope (E) protein protomers. ZIKV neutralization by this antibody is presumably accomplished by cross-linking the E proteins, which likely prevents formation of E protein trimers required for fusion of the viral and cellular membranes. A single dose of ZIKV-195 administered 5 days after virus inoculation showed marked protection against lethality in a stringent mouse model of infection.
Zika 病毒（ZIKV）是黄病毒科黄病毒属的一种主要的人类病原体。与大多数其他经昆虫传播的黄病毒不同，ZIKV 还可以在人与人之间通过性传播和母婴传播。在最近的疫情中，ZIKV 感染与小头畸形、先天性疾病和格林-巴利综合征有关。中和抗体具有作为治疗剂的潜力。我们在此报告了 Zika 病毒病毒粒子与强效中和人源单克隆抗体 ZIKV-195 的 Fab 片段复合物的 4Å 分辨率冷冻电镜结构。ZIKV-195 Fab 片段的结合足迹扩展到两个相邻的包膜（E）蛋白三聚体上。这种抗体对 Zika 病毒的中和作用可能是通过交联 E 蛋白来实现的，这可能阻止了形成融合病毒和细胞膜所需的 E 蛋白三聚体。在严格的感染小鼠模型中，在病毒接种后 5 天给予单次剂量的 ZIKV-195 显示出对致死性的显著保护作用。
