Shao Yaozhong, Qi Ying, Huang Yujing, Liu Zhongyang, Ma Yanping, Guo Xin, Jiang Shujuan, Sun Zhengrong, Ruan Qiang
Virus Laboratory, Affiliated Shengjing Hospital, China Medical University, Shenyang, Liaoning 110004, China.
J Biosci. 2016 Jun;41(2):183-92. doi: 10.1007/s12038-016-9605-1.
Human cytomegalovirus (HCMV) can cause congenital diseases and opportunistic infections in immunocompromised individuals. Its functional proteins and microRNAs (miRNAs) facilitate efficient viral propagation by altering host cell behaviour. Identification of functional target genes of miRNAs is an important step in studies on HCMV pathogenesis. In this study, Glutaminyl-tRNA Synthetase (QARS), which could regulate signal transduction pathways for cellular apoptosis, was identified as a direct target of hcmv-miR-US4-1. Apoptosis assay revealed that as silence of QARS by ectopic expression of hcmv-miR-US4-1 and specific small interference RNA of QARS can promote cell apoptosis in HCMV-infected HELF cells. Moreover, viral growth curve assays showed that hcmv-miR-US4-1 benefits the discharge of infectious virus particles. However, silence of hcmv-miR-US4-1 by its specific inhibitor overturned these effects. These results imply that hcmv-miR-US4-1 might have the same effects during HCMV nature infection. In general, hcmv-miR-US4-1 may involve in promoting cell apoptosis and benefiting discharge of infectious virus particles via down-regulation of QARS in HCMV-infected HELF cells.
人巨细胞病毒（HCMV）可导致先天性疾病，并在免疫功能低下的个体中引发机会性感染。其功能蛋白和微小RNA（miRNA）通过改变宿主细胞行为促进病毒的有效传播。鉴定miRNA的功能靶基因是HCMV发病机制研究中的重要一步。在本研究中，可调节细胞凋亡信号转导途径的谷氨酰胺-tRNA合成酶（QARS）被鉴定为hcmv-miR-US4-1的直接靶标。凋亡分析显示，通过异位表达hcmv-miR-US4-1和QARS的特异性小干扰RNA使QARS沉默，可促进HCMV感染的人胚肺成纤维细胞（HELF）凋亡。此外，病毒生长曲线分析表明，hcmv-miR-US4-1有利于感染性病毒颗粒的释放。然而，用其特异性抑制剂沉默hcmv-miR-US4-1可逆转这些效应。这些结果表明，hcmv-miR-US4-1在HCMV自然感染过程中可能具有相同的作用。总体而言，hcmv-miR-US4-1可能通过下调HCMV感染的HELF细胞中的QARS，参与促进细胞凋亡和有利于感染性病毒颗粒的释放。
