D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Sci Rep. 2017 Jan 23;7:40780. doi: 10.1038/srep40780.
Zika virus (ZIKV) has been associated with microcephaly and other brain abnormalities; however, the molecular consequences of ZIKV to human brain development are still not fully understood. Here we describe alterations in human neurospheres derived from induced pluripotent stem (iPS) cells infected with the strain of Zika virus that is circulating in Brazil. Combining proteomics and mRNA transcriptional profiling, over 500 proteins and genes associated with the Brazilian ZIKV infection were found to be differentially expressed. These genes and proteins provide an interactome map, which indicates that ZIKV controls the expression of RNA processing bodies, miRNA biogenesis and splicing factors required for self-replication. It also suggests that impairments in the molecular pathways underpinning cell cycle and neuronal differentiation are caused by ZIKV. These results point to biological mechanisms implicated in brain malformations, which are important to further the understanding of ZIKV infection and can be exploited as therapeutic potential targets to mitigate it.
寨卡病毒（ZIKV）与小头症和其他脑异常有关；然而，寨卡病毒对人类大脑发育的分子后果仍不完全清楚。在这里，我们描述了由诱导多能干细胞（iPS）衍生的神经球的改变，这些细胞感染了在巴西流行的寨卡病毒株。结合蛋白质组学和 mRNA 转录谱分析，发现与巴西寨卡病毒感染相关的 500 多种蛋白质和基因表达水平存在差异。这些基因和蛋白质提供了一个相互作用图谱，表明寨卡病毒控制着 RNA 加工体、miRNA 生物发生和自我复制所需的剪接因子的表达。这也表明，寨卡病毒会损害细胞周期和神经元分化的分子途径。这些结果指出了与脑畸形相关的生物学机制，这对于进一步了解寨卡病毒感染很重要，并可以作为治疗的潜在靶点来减轻其影响。
