Othumpangat Sreekumar, Noti John D, Beezhold Donald H
Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV, USA.
Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV, USA.
Virology. 2014 Nov;468-470:256-264. doi: 10.1016/j.virol.2014.08.007. Epub 2014 Sep 7.
Influenza virus infection induces several changes in host miRNA profile, host cell death and tissue damage. Cytochrome c is a regulator of the intrinsic apoptotic pathway and is altered during viral infections. Within the first 3h of infection with influenza virus, significant down-regulation of hsa-miRNA-4276 (miRNA-4276) is followed by a 2-fold increase in cytochrome c oxidase VIC (COX6C) mRNA was found to occur in human alveolar and bronchial epithelial cells. Expression of caspase-9 also increased within the first 3h of infection, but subsequently decreased. Modulation of miR-4276 using mimic and inhibitor oligonucleotides showed significant down-regulation or up-regulation, respectively, of COX6C expression. Our data suggests that on initial exposure to influenza virus, host cells upregulate COX6C mRNA expression through silencing miR-4276 and repressed viral replication by inducing the apoptotic protein caspase-9. Taken together, these data suggest that miR-4276 may be an important regulator of the early stages of infection by influenza.
流感病毒感染会引起宿主微小RNA（miRNA）谱、宿主细胞死亡和组织损伤的多种变化。细胞色素c是内源性凋亡途径的调节因子，在病毒感染期间会发生改变。在流感病毒感染的最初3小时内，人肺泡和支气管上皮细胞中发现hsa-miRNA-4276（miRNA-4276）显著下调，随后细胞色素c氧化酶VIC（COX6C）mRNA增加了2倍。半胱天冬酶-9的表达在感染的最初3小时内也增加，但随后下降。使用模拟物和抑制剂寡核苷酸对miR-4276进行调节，分别显示COX6C表达显著下调或上调。我们的数据表明，在初次接触流感病毒时，宿主细胞通过沉默miR-4276上调COX6C mRNA表达，并通过诱导凋亡蛋白半胱天冬酶-9来抑制病毒复制。综上所述，这些数据表明miR-4276可能是流感感染早期阶段的重要调节因子。
