Asian Zika Virus Isolate Significantly Changes the Transcriptional Profile and Alternative RNA Splicing Events in a Neuroblastoma Cell Line
Asian Zika Virus Isolate Significantly Changes the Transcriptional Profile and Alternative RNA Splicing Events in a Neuroblastoma Cell Line
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DOI：
10.3390/v12050510
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发表时间：
2020-05-01
期刊：
影响因子：
4.7
通讯作者：
Pager, Cara T.
中科院分区：
文献类型：
--
作者：
Bonenfant, Gaston;Meng, Ryan;Pager, Cara T.
前体mRNA的选择性剪接扩展了单个遗传蓝图以编码多种功能多样的蛋白质同种型。病毒先前已被证明与宿主剪接机制相互作用，依赖于宿主剪接机制并改变宿主剪接机制。然而，病毒感染对全球替代切片（AS）景观的影响却未得到充分重视。在这里，我们研究了感染当代波多黎各寨卡病毒（ZIKV（PR））分离株，原型乌干达ZIKV（ZIKV（MR））分离株和登革热病毒2（DENV 2）的神经元细胞的转录和选择性剪接谱。我们的分析显示，与ZIKV（MR）或DENV 2相比，ZIKV（PR）诱导表达基因的显著更多差异变化，尽管所有三种病毒均显示出等同的感染性和病毒RNA水平。与转录谱一致，与ZIKV（MR）或DENV2相比，ZIKV（PR）诱导了更高数量的选择性剪接事件，并且基因本体分析突出了与mRNA剪接相关的基因中的选择性剪接变化。总之，我们表明ZIKV不仅在转录水平上而且通过细胞转录物的选择性剪接影响细胞RNA稳态。这些发现可以为与这种病毒相关的神经病理学提供新的分子见解。
The alternative splicing of pre-mRNAs expands a single genetic blueprint to encode multiple, functionally diverse protein isoforms. Viruses have previously been shown to interact with, depend on, and alter host splicing machinery. The consequences, however, incited by viral infection on the global alternative slicing (AS) landscape are under-appreciated. Here, we investigated the transcriptional and alternative splicing profile of neuronal cells infected with a contemporary Puerto Rican Zika virus (ZIKV(PR)) isolate, an isolate of the prototypical Ugandan ZIKV (ZIKV(MR)), and dengue virus 2 (DENV2). Our analyses revealed that ZIKV(PR) induced significantly more differential changes in expressed genes compared to ZIKV(MR) or DENV2, despite all three viruses showing equivalent infectivity and viral RNA levels. Consistent with the transcriptional profile, ZIKV(PR) induced a higher number of alternative splicing events compared to ZIKV(MR) or DENV2, and gene ontology analyses highlighted alternative splicing changes in genes associated with mRNA splicing. In summary, we show that ZIKV affects cellular RNA homeostasis not only at the transcriptional levels but also through the alternative splicing of cellular transcripts. These findings could provide new molecular insights into the neuropathologies associated with this virus.