Respiratory syncytial virus regulates human microRNAs by using mechanisms involving beta interferon and NF-κB.
Respiratory syncytial virus regulates human microRNAs by using mechanisms involving beta interferon and NF-κB.
复制标题
DOI：
10.1128/mbio.00220-12
复制
发表时间：
2012-12-18
期刊：
影响因子：
6.4
通讯作者：
Crowe JE Jr
中科院分区：
文献类型：
--
作者：
Thornburg NJ;Hayward SL;Crowe JE Jr
呼吸道合胞病毒（RSV）是婴儿和儿童严重下呼吸道疾病最常见的病毒原因。该病毒在气道中的极化上皮细胞中复制，并且在较小程度上感染气道抗原呈递细胞，例如树突状细胞（DC）。RSV具有许多表达的基因，其拮抗I型干扰素和抑制复制效率的其它相关宿主因子途径的作用。病毒感染通过特异性拮抗宿主蛋白质的功能、通过诱导RNA应激颗粒以及通过诱导宿主基因表达模式的改变来改变宿主基因转录和宿主转录物的翻译。在健康细胞中，微小RNA（miRNAs）通过靶向mRNA分子的非编码区以引起转录物的沉默或降解来调节基因表达。目前尚不清楚RSV感染是否会改变细胞中microRNA的水平。我们分析了RSV感染的上皮细胞或DC中宿主细胞microRNA的表达模式，发现RSV确实改变了microRNA的表达，但以细胞类型特异性的方式。研究表明，let-7 b在DC中上调，而let-7i和miR-30 b在上皮细胞中上调，这需要病毒复制。有趣的是，我们发现RSV非结构基因NS 1和NS 2拮抗let-7i和miR-30 b的上调。RSV似乎通过调节与干扰素应答相关的miRNA的表达来操纵宿主细胞基因表达。这些数据表明，副粘病毒的病毒-宿主细胞相互作用的新机制。呼吸道合胞病毒（RSV）是婴儿和儿童严重下呼吸道疾病的最常见原因。人类先天性免疫应答在接种后早期抑制RSV复制，主要是通过称为干扰素的物质的作用。然而，该病毒已经发展了几种机制来抵消宿主的先天免疫反应。目前还不清楚RSV感染是否会改变宿主microRNA的表达，microRNA是转录后调节因子的短RNA序列。这篇论文表明，RSV确实诱导了与NF-κB通路或干扰素通路相关的独特microRNA表达模式。microRNA谱根据感染的细胞类型（气道细胞或抗原呈递细胞）而不同。有趣的是，病毒似乎通过在细胞中表达减少microRNA诱导的非结构病毒基因来抵消microRNA反应。这些数据表明副粘病毒调节宿主细胞对感染的反应的一种新方式。
Respiratory syncytial virus (RSV) is the most common viral cause of severe lower respiratory tract illness in infants and children. The virus replicates in polarized epithelial cells in the airway and, to a lesser extent, infects airway antigen-presenting cells, such as dendritic cells (DCs). RSV possesses a number of expressed genes that antagonize the effect of type I interferons and other related host factor pathways that inhibit replication efficiency. Virus infection alters host gene transcription and the translation of host transcripts through specific antagonism of the function of host proteins, through induction of RNA stress granules, and through induction of altered patterns of host gene expression. In healthy cells, microRNAs (miRNAs) regulate gene expression by targeting the noncoding region of mRNA molecules to cause silencing or degradation of transcripts. It is not known whether or not RSV infection alters the level of microRNAs in cells. We profiled the pattern of expression of host cell microRNAs in RSV-infected epithelial cells or DCs and found that RSV did alter microRNA expression but in a cell-type-specific manner. The studies showed that let-7b was upregulated in DCs, while let-7i and miR-30b were upregulated in epithelial cells in a process that required viral replication. Interestingly, we found that the RSV nonstructural genes NS1 and NS2 antagonized the upregulation of let-7i and miR-30b. RSV appears to manipulate host cell gene expression through regulation of expression of miRNAs related to the interferon response. The data suggest a new mechanism of virus-host cell interactions for paramyxoviruses. Respiratory syncytial virus (RSV) is the most common cause of serious lower respiratory tract illness in infants and children. The human innate immune response inhibits RSV replication early after inoculation, principally through the effect of substances called interferons. The virus, however, has developed several mechanisms for counteracting the host innate immune response. It is not known whether or not RSV infection alters the expression of host microRNAs, which are short RNA sequences that are posttranscriptional regulators. This paper shows that RSV does induce unique patterns of microRNA expression related to the NF-κB pathway or interferon pathways. The microRNA profiles differed depending on the cell type that was infected, airway cell or antigen-presenting cell. Interestingly, the virus appears to counteract the microRNA response by expressing nonstructural viral genes in the cell that reduce microRNA induction. The data suggest a new way in which paramyxoviruses regulate the host cell response to infection.