Human cytomegalovirus latent infection alters the expression of cellular and viral microRNA

Human cytomegalovirus latent infection alters the expression of cellular and viral microRNA
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人类巨细胞病毒潜伏感染改变细胞和病毒 microRNA 的表达

DOI:
10.1016/j.gene.2013.12.012
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发表时间:
2014-02-25
期刊:
影响因子:
3.5
通讯作者:
Zheng, Xiaoqun
Zheng, Xiaoqun
中科院分区:
生物学3区
文献类型:
--
作者:
Fu, Miao;Gao, Yan;Zheng, Xiaoqun

文献摘要

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背景:microRNAs(MiRNAs)在植物、动物和病毒的基因表达调控中发挥着重要作用。宿主和病毒miRNA的全面表征将有助于揭示人类巨细胞病毒(HCMV)潜伏感染进展的分子机制。为了研究HCIVIV和宿主细胞在潜伏感染过程中的miRNA表达谱,我们对从HCMV感染和模拟感染的人单核细胞白血病细胞系THP-1分离的小RNA进行了深度测序。结果:利用THP-1细胞建立了HCMV潜伏感染细胞模型。利用高通量测序技术对HCMV感染和模拟感染的THP-1的小RNA文库进行测序,并研究它们的小RNA转录本。我们发现8个miRNAs包括miR-US25-1、miR-1JS25-2-5p和miR-UL112在HCMV潜伏感染过程中表达。宿主miRNAs的表达也受HCMV潜伏感染的影响。至少有49个细胞miRNAs差异表达:其中39个在HCMV潜伏感染时上调,10个下调。人miRNA hsamiR-124-3p在HCMV潜伏感染文库中的表达显著上调。此外,我们在HCMV感染和模拟感染的THP-1文库中发现了14个细胞内新的miRNAs。对差异表达的miRNAs靶基因的功能注释表明,大多数基因参与了黑素合成、肿瘤途径、内吞作用和WNT信号通路。结论:本研究获得的小RNA转录本表明,深度测序结合生物信息学方法对于了解宿主和病毒小RNAs在HCMV潜伏感染中的表达和功能是有用的。这种方法也可以应用于其他类型的病毒的研究。(C)2013爱思唯尔B.V.保留所有权利。
Background: MicroRNAs (miRNAs) play important roles in regulating gene expression of plants, animals and viruses. Comprehensive characterization of host and viral miRNA will help uncover the molecular mechanisms that underlie the progression of human cytomegalovirus (HCMV) latent infection. To investigate the miRNA expression profile of HCIVIV and host cells during latent infection, we performed deep-sequencing analysis of the small RNAs isolated from HCMV-infected and mock-infected human monocytic leukemia cell line, THP-1.Results: We established a HCMV latent infection cell model using the THP-1 cells. High-throughput sequencing technology was used to sequence small RNA libraries of the HCMV-infected and mock-infected THP-1 and to investigate their small RNA transcriptomes. We found eight miRNAs including miR-US25-1, miR-1JS25-2-5p and miR-UL112 that were expressed by HCMV during latent infection. The expressions of the host miRNAs were also affected by HCMV latent infection. At least 49 cellular miRNAs were differentially expressed: 39 were upregulated and 10 were down-regulated upon HCMV latent infection. The expression of the human miRNA hsamiR-124-3p was significantly up-regulated in the HCMV latent infection library. In addition, we found 14 cellular novel miRNAs in the HCMV-infected and mock-infected THP-1 libraries. Functional annotation of the target genes of the differentially expressed miRNAs suggested that the majority of the genes are involved in melanogenesis, pathways in cancer, endocytosis and wnt signaling pathway.Conclusions: The small RNA transcriptomes obtained in this study demonstrate the usefulness of the deepsequencing combined with bioinformatics approach in understanding of the expression and function of host and viral small RNAs in HCMV latent infection. This approach can also be applied to the study of other kinds of viruses. (C) 2013 Elsevier B.V. All rights reserved.