Respiratory syncytial virus modifies microRNAs regulating host genes that affect virus replication.
Respiratory syncytial virus modifies microRNAs regulating host genes that affect virus replication.
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DOI：
10.1099/vir.0.044255-0
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发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Tripp RA
中科院分区：
文献类型：
--
作者：
Bakre A;Mitchell P;Coleman JK;Jones LP;Saavedra G;Teng M;Tompkins SM;Tripp RA
呼吸道合胞病毒（RSV）在婴幼儿和老年人中引起大量发病率和危及生命的下呼吸道疾病。了解宿主对RSV感染的反应对于开发疾病干预方法至关重要。microRNAs （miRNAs）在应答RSV感染的宿主基因转录后调控中的作用尚不清楚。本研究表明，RSV感染人肺泡上皮细胞系（A549）诱导了5种mirna (let-7f、miR-24、miR-337-3p、miR-26b和miR-520a-5p)，抑制了2种mirna (miR-198和miR-595)，并表明RSV G蛋白触发了let-7f的表达。荧光素酶非翻译区报告者和miRNA模拟物和抑制剂验证了预测的靶标，包括细胞周期基因（CCND1， DYRK2和ELF4），趋化因子基因（CCL7）和细胞因子信号传导3基因抑制因子（SOCS3）。利用miRNA模拟物和抑制剂调节let-7家族miRNA水平影响RSV复制，表明RSV通过调节宿主miRNA表达来影响宿主抗病毒应答的结果，这在一定程度上是通过RSV G蛋白表达介导的。
Respiratory syncytial virus (RSV) causes substantial morbidity and life-threatening lower respiratory tract disease in infants, young children and the elderly. Understanding the host response to RSV infection is critical for developing disease-intervention approaches. The role of microRNAs (miRNAs) in post-transcriptional regulation of host genes responding to RSV infection is not well understood. In this study, it was shown that RSV infection of a human alveolar epithelial cell line (A549) induced five miRNAs (let-7f, miR-24, miR-337-3p, miR-26b and miR-520a-5p) and repressed two miRNAs (miR-198 and miR-595), and showed that RSV G protein triggered let-7f expression. Luciferase–untranslated region reporters and miRNA mimics and inhibitors validated the predicted targets, which included cell-cycle genes (CCND1, DYRK2 and ELF4), a chemokine gene (CCL7) and the suppressor of cytokine signalling 3 gene (SOCS3). Modulating let-7 family miRNA levels with miRNA mimics and inhibitors affected RSV replication, indicating that RSV modulates host miRNA expression to affect the outcome of the antiviral host response, and this was mediated in part through RSV G protein expression.
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