Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857, Singapore.
Centre for BioImaging Sciences, Department of Biological Sciences, National University of Singapore, Singapore 117557, Singapore.
Nature. 2016 May 19;533(7603):425-8. doi: 10.1038/nature17994. Epub 2016 Apr 19.
Zika virus (ZIKV), formerly a neglected pathogen, has recently been associated with microcephaly in fetuses, and with Guillian-Barré syndrome in adults. Here we present the 3.7 Å resolution cryo-electron microscopy structure of ZIKV, and show that the overall architecture of the virus is similar to that of other flaviviruses. Sequence and structural comparisons of the ZIKV envelope (E) protein with other flaviviruses show that parts of the E protein closely resemble the neurovirulent West Nile and Japanese encephalitis viruses, while others are similar to dengue virus (DENV). However, the contribution of the E protein to flavivirus pathobiology is currently not understood. The virus particle was observed to be structurally stable even when incubated at 40 °C, in sharp contrast to the less thermally stable DENV. This is also reflected in the infectivity of ZIKV compared to DENV serotypes 2 and 4 (DENV2 and DENV4) at different temperatures. The cryo-electron microscopy structure shows a virus with a more compact surface. This structural stability of the virus may help it to survive in the harsh conditions of semen, saliva and urine. Antibodies or drugs that destabilize the structure may help to reduce the disease outcome or limit the spread of the virus.
寨卡病毒（ZIKV），以前是一种被忽视的病原体，最近与胎儿小头畸形和成人吉兰-巴雷综合征有关。在这里，我们呈现了寨卡病毒的 3.7Å 分辨率冷冻电镜结构，并表明该病毒的整体结构与其他黄病毒相似。寨卡病毒包膜（E）蛋白的序列和结构比较与其他黄病毒表明，E 蛋白的某些部分与神经毒力的西尼罗河和日本脑炎病毒非常相似，而其他部分则与登革热病毒（DENV）相似。然而，E 蛋白对黄病毒发病机制的贡献目前尚不清楚。即使在 40°C 下孵育，病毒颗粒也观察到结构稳定，与不太耐热的 DENV 形成鲜明对比。这也反映在不同温度下，与 DENV 血清型 2 和 4（DENV2 和 DENV4）相比，寨卡病毒的感染力。冷冻电镜结构显示出一种具有更紧凑表面的病毒。该病毒的结构稳定性可能有助于其在精液、唾液和尿液等恶劣条件下存活。使结构不稳定的抗体或药物可能有助于降低疾病结果或限制病毒的传播。
