Structure of the thermally stable Zika virus
Structure of the thermally stable Zika virus
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DOI：
10.1038/nature17994
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发表时间：
2016-05-19
期刊：
影响因子：
64.8
通讯作者：
Lok, Shee-Mei
中科院分区：
文献类型：
--
作者：
Kostyuchenko, Victor A.;Lim, Elisa X. Y.;Lok, Shee-Mei
寨卡病毒（ZIKV）以前是一种被忽视的病原体，最近与胎儿的小头畸形（1）和成人的格林-巴利综合征（2）有关。在这里，我们展示了ZIKV的3.7埃分辨率冷冻电子显微镜结构，并表明该病毒的整体结构与其他黄病毒相似。ZIKV包膜（E）蛋白与其他黄病毒的序列和结构比较表明，E蛋白的部分与神经毒性西尼罗河病毒和日本脑炎病毒非常相似，而其他蛋白则与登革热病毒（DENV）相似。然而，E蛋白对黄病毒病理学的贡献目前尚不清楚。观察到病毒颗粒即使在40摄氏度下孵育时也是结构稳定的，与热稳定性较差的DENV 3形成鲜明对比。这也反映在不同温度下ZIKV与DENV血清型2和4（DENV 2和DENV 4）相比的感染性中。冷冻电子显微镜结构显示病毒具有更紧密的表面。病毒的这种结构稳定性可能有助于它在精液（4），唾液（5）和尿液（6）的恶劣条件下存活。使结构不稳定的抗体或药物可能有助于减少疾病的结果或限制病毒的传播。
Zika virus (ZIKV), formerly a neglected pathogen, has recently been associated with microcephaly in fetuses(1), and with Guillian-Barre syndrome in adults(2). Here we present the 3.7 angstrom resolution cryoelectron 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 degrees C, in sharp contrast to the less thermally stable DENV3. This is also reflected in the infectivity of ZIKV compared to DENV serotypes 2 and 4 (DENV2 and DENV4) at different temperatures. The cryoelectron 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(4), saliva(5) and urine(6). Antibodies or drugs that destabilize the structure may help to reduce the disease outcome or limit the spread of the virus.