Temporal Landscape of MicroRNA-Mediated Host-Virus Crosstalk during Productive Human Cytomegalovirus Infection
Temporal Landscape of MicroRNA-Mediated Host-Virus Crosstalk during Productive Human Cytomegalovirus Infection
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DOI：
10.1016/j.chom.2015.05.014
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发表时间：
2015-06-10
影响因子：
30.3
通讯作者：
Ahn, Kwangseog
中科院分区：
文献类型：
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作者：
Kim, Sungchul;Seo, Daekwan;Ahn, Kwangseog
生产性病毒感染过程中的miRNA活性的时间分布可以提供宿主-病毒相互作用的基本见解。在病毒感染的背景下，大多数报道的miRNA靶组分析已经在潜伏感染的细胞中进行，并且缺乏用于定量特定miRNA靶位点处的抑制功效的可靠模型。在这里，我们通过使用AGO-CLIP-seq以及生物信息学方法（称为ACE评分）来定量特定靶位点处的miRNA功能，从而在裂解性HCMV感染期间鉴定出高度胜任的时间miRNA靶向体。靶位点的抑制效率与ACE评分的大小相关，并且通过ACE评分鉴定的时间HCMV编码的miRNA靶向组在HCMV生物学中心途径中涉及的功能类别中显著富集。此外，人类和病毒miRNA靶向组之间的比较分析支持它们之间存在密切合作和共同靶向。我们的整体调查提供了一个有价值的资源，了解宿主病毒的相互作用，在裂解HCMV感染。
Temporal profiles of miRNA activity during productive virus infection can provide fundamental insights into host-virus interactions. Most reported miRNA targetome analyses in the context of virus infection have been performed in latently infected cells and lack reliable models for quantifying the suppression efficacy at specific miRNA target sites. Here, we identified highly competent temporal miRNA targetomes during lytic HCMV infection by using AGO-CLIP-seq together with a bioinformatic method that quantifies miRNA functionality at a specific target site, called ACE-scoring. The repression efficiency at target sites correlates with the magnitude of the ACE-score, and temporal HCMV-encoded miRNA targetomes identified by ACE-scoring were significantly enriched in functional categories involved in pathways central for HCMV biology. Furthermore, comparative analysis between human and viral miRNA targetomes supports the existence of intimate cooperation and co-targeting between them. Our holistic survey provides a valuable resource for understanding host-virus interactions during lytic HCMV infection.