Despite efforts to elucidate Zika virus (ZIKV) teratogenesis, still several issues remain unresolved, particularly on the molecular mechanisms behind the pathogenesis of Congenital Zika Syndrome (CZS). To answer this question, we used bioinformatics tools, animal experiments and human gene expression analysis to investigate genes related to brain development potentially involved in CZS. Searches in databases for genes related to brain development and CZS were performed, and a protein interaction network was created. The expression of these genes was analyzed in a CZS animal model and secondary gene expression analysis (DGE) was performed in human cells exposed to ZIKV. A total of 2610 genes were identified in the databases, of which 1013 were connected. By applying centrality statistics of the global network, 36 candidate genes were identified, which, after selection resulted in nine genes. Gene expression analysis revealed distinctive expression patterns for , , , as well as for and in the CZS model. Furthermore, DGE analysis altered expression of , . In conclusion, systems biology are helpful tools to identify candidate genes to be validated in vitro and in vivo. , , , , and have altered expression in ZIKV-induced brain malformations.

中文翻译：

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可能参与寨卡病毒致畸作用的新候选基因

尽管人们努力阐明寨卡病毒（ZIKV）致畸作用，但仍有几个问题尚未解决，特别是先天性寨卡综合症（CZS）发病机制背后的分子机制。为了回答这个问题，我们使用生物信息学工具、动物实验和人类基因表达分析来研究与 CZS 可能涉及的大脑发育相关的基因。在数据库中搜索与大脑发育和 CZS 相关的基因，并创建了蛋白质相互作用网络。在 CZS 动物模型中分析了这些基因的表达，并在暴露于 ZIKV 的人类细胞中进行了二次基因表达分析 (DGE)。数据库中总共鉴定出2610个基因，其中1013个是相连的。通过应用全球网络的中心性统计，确定了 36 个候选基因，经过选择后产生了 9 个基因。基因表达分析揭示了 CZS 模型中 、 、 以及 和 的独特表达模式。此外，DGE 分析改变了 、 的表达。总之，系统生物学是识别待体外和体内验证的候选基因的有用工具。 、 、 、 和 在 ZIKV 诱导的脑畸形中表达发生改变。