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深度RNA测序揭示了与人类成纤维细胞对单纯疱疹病毒1感染的细胞反应相关的环状RNA文库。

Deep RNA Sequencing Reveals a Repertoire of Human Fibroblast Circular RNAs Associated with Cellular Responses to Herpes Simplex Virus 1 Infection.

作者信息

Shi Jiandong, Hu Ningzhu, Mo Ling, Zeng Zhaoping, Sun Jing, Hu Yunzhang

机构信息

Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.

Yunnan Key Laboratory of Vaccine Research and Development of Severe Infectious Disease, Kunming, China.

出版信息

Cell Physiol Biochem. 2018;47(5):2031-2045. doi: 10.1159/000491471. Epub 2018 Jul 4.

DOI:10.1159/000491471
PMID:29972822
Abstract

BACKGROUND/AIMS: Circular RNAs (circRNAs), a new class of regulators of gene expression, are involved in diverse physiological and pathogenic processes. However, their role in cellular responses to virus infection is yet unclear.

METHODS

A human lung fibroblast cell line was infected or mock infected by herpes simplex virus 1 (HSV-1). Deep RNA sequencing was used to profile the global changes in circRNAs, genes, and miRNAs following HSV-1 infection. Altered circRNAs, genes, and miRNAs were validated using quantitative reverse transcription polymerase chain reaction (RT-qPCR). An integration analysis of circRNAs, genes, and miRNAs was applied to investigate the putative function of the dysregulated circRNAs.

RESULTS

A total of 536 circRNAs, 3,885 genes, and 207 miRNAs were significantly dysregulated after HSV-1 infection. An integration analysis of circRNAs, genes, and miRNAs revealed the alleged involvement of dysregulated circRNAs in cellular responses to HSV-1 infection via the circRNA-miRNA-gene regulatory axis. These genes regulated by circRNAs were enriched to NOD-like receptor/JAK-STAT signaling pathway, and pathways of apoptosis, cell cycle progression, and cell death, all of which may be implicated in the viral pathogenesis and cellular immunity.

CONCLUSIONS

These data present a comprehensive view for circRNAs induced by HSV-1 and their interplay with miRNAs and genes during HSV-1 infection, thus offering new insights into the mechanisms of interactions between HSV-1 and the host.

摘要

背景/目的:环状RNA(circRNAs)作为一类新的基因表达调节因子,参与多种生理和致病过程。然而,它们在细胞对病毒感染的反应中的作用尚不清楚。

方法

用人单纯疱疹病毒1型(HSV-1)感染或模拟感染人肺成纤维细胞系。采用深度RNA测序分析HSV-1感染后circRNAs、基因和miRNAs的整体变化。使用定量逆转录聚合酶链反应(RT-qPCR)验证circRNAs、基因和miRNAs的变化。通过circRNAs、基因和miRNAs的整合分析来研究失调的circRNAs的假定功能。

结果

HSV-1感染后,共有536个circRNAs、3885个基因和207个miRNAs发生显著失调。circRNAs、基因和miRNAs的整合分析显示,失调的circRNAs可能通过circRNA-miRNA-基因调控轴参与细胞对HSV-1感染的反应。这些受circRNAs调控的基因富集到NOD样受体/JAK-STAT信号通路以及凋亡、细胞周期进程和细胞死亡通路,所有这些都可能与病毒发病机制和细胞免疫有关。

结论

这些数据全面展示了HSV-1诱导的circRNAs及其在HSV-1感染过程中与miRNAs和基因的相互作用,从而为HSV-1与宿主之间的相互作用机制提供了新的见解。

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