Gong Danyang, Zhang Tian-Hao, Zhao Dawei, Du Yushen, Chapa Travis J, Shi Yuan, Wang Laurie, Contreras Deisy, Zeng Gang, Shi Pei-Yong, Wu Ting-Ting, Arumugaswami Vaithilingaraja, Sun Ren
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA.
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
iScience. 2018 Mar 23;1:97-111. doi: 10.1016/j.isci.2018.02.005.
Zika virus (ZIKV) infection causes Guillain-Barré syndrome and severe birth defects. ZIKV envelope (E) protein is the major viral protein involved in cell receptor binding and entry and is therefore considered one of the major determinants in ZIKV pathogenesis. Here we report a gene-wide mapping of functional residues of ZIKV E protein using a mutant library, with changes covering every nucleotide position. By comparing the replication fitness of every viral mutant between mosquito and human cells, we identified that mutations affecting glycosylation display the most divergence. By characterizing individual mutants, we show that ablation of glycosylation selectively benefits ZIKV infection of mosquito cells by enhancing cell entry, whereas it either has little impact on ZIKV infection on certain human cells or leads to decreased infection through the entry factor DC-SIGN. In conclusion, we define the roles of individual residues of ZIKV envelope protein, which contribute to ZIKV replication fitness in human and mosquito cells.
寨卡病毒（ZIKV）感染会导致格林-巴利综合征和严重的出生缺陷。寨卡病毒包膜（E）蛋白是参与细胞受体结合和进入的主要病毒蛋白，因此被认为是寨卡病毒发病机制的主要决定因素之一。在此，我们报告了使用突变体文库对寨卡病毒E蛋白功能残基进行的全基因图谱绘制，突变覆盖了每个核苷酸位置。通过比较蚊子和人类细胞中每个病毒突变体的复制适应性，我们发现影响糖基化的突变表现出最大的差异。通过对单个突变体进行表征，我们表明糖基化缺失通过增强细胞进入选择性地有利于寨卡病毒在蚊子细胞中的感染，而它对寨卡病毒在某些人类细胞中的感染影响很小，或者通过进入因子DC-SIGN导致感染减少。总之，我们确定了寨卡病毒包膜蛋白单个残基的作用，这些残基有助于寨卡病毒在人类和蚊子细胞中的复制适应性。
