University of Texas Medical Branch at Galveston, Department of Pediatrics, Galveston, 77555, USA.
University of Texas Medical Branch at Galveston, Department of Biochemistry and Molecular Biology, Galveston, 77555, USA.
Sci Rep. 2018 Jan 10;8(1):387. doi: 10.1038/s41598-017-18672-5.
Exosomes are microvesicles known to carry biologically active molecules, including RNA, DNA and proteins. Viral infections can induce profound changes in exosome composition, and exosomes have been implicated in viral transmission and pathogenesis. No information is current available regarding exosome composition and function during infection with Respiratory Syncytial Virus (RSV), the most important cause of lower respiratory tract infections in children. In this study, we characterized exosomes released from RSV-infected lung carcinoma-derived A549 cells. RNA deep sequencing revealed that RSV exosomes contain a diverse range of RNA species like messenger and ribosomal RNA fragments, as well as small noncoding RNAs, in a proportion different from exosomes isolated from mock-infected cells. We observed that both RNA and protein signatures of RSV were present in exosomes, however, they were not able to establish productive infection in uninfected cells. Exosomes isolated from RSV-infected cells were able to activate innate immune response by inducing cytokine and chemokine release from human monocytes and airway epithelial cells. These data suggest that exosomes may play an important role in pathogenesis or protection against disease, therefore understating their role in RSV infection may open new avenues for target identification and development of novel therapeutics.
外泌体是已知携带生物活性分子的微小囊泡，包括 RNA、DNA 和蛋白质。病毒感染可诱导外泌体组成发生深刻变化，外泌体已被牵涉到病毒传播和发病机制中。目前尚无关于呼吸道合胞病毒 (RSV) 感染期间外泌体组成和功能的信息，RSV 是儿童下呼吸道感染的最重要原因。在这项研究中，我们对 RSV 感染的肺腺癌衍生 A549 细胞释放的外泌体进行了表征。RNA 深度测序显示，RSV 外泌体包含多种 RNA 种类，如信使 RNA 和核糖体 RNA 片段，以及小非编码 RNA，其比例与来自模拟感染细胞的外泌体不同。我们观察到，RSV 的 RNA 和蛋白质特征都存在于外泌体中，但它们不能在未感染的细胞中建立有效的感染。从 RSV 感染细胞中分离出的外泌体能够通过诱导人单核细胞和气道上皮细胞释放细胞因子和趋化因子来激活先天免疫反应。这些数据表明，外泌体可能在发病机制或疾病保护中发挥重要作用，因此了解它们在 RSV 感染中的作用可能为靶标识别和新型治疗药物的开发开辟新途径。
