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Japanese Encephalitis Virus exploits microRNA-155 to suppress the non-canonical NF-κB pathway in human microglial cells
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms ( IF 2.6 ) Pub Date : 2020-09-26 , DOI: 10.1016/j.bbagrm.2020.194639
Meghana Rastogi , Sunit Kumar Singh

Japanese Encephalitis Virus (JEV) is a single positive strand RNA virus, belongs to the Flaviviridae family. JEV is neurotropic in nature which accounts for 30–50% neurological, psychiatric sequelae and movement disorder, with 20–30% case fatality rate among children or elder population. JEV causes neuronal loss and microglial activation which leads to neuroinflammation. The microRNAs are the molecular switches, which regulate the gene expression post-transcriptionally. The microRNA-155 has been reported to be associated with CNS-related pathologies like, experimental autoimmune encephalitis, multiple sclerosis and amyotrophic lateral sclerosis. In the present study, we infected microglial cells with JEV, which resulted in the up-regulation of microRNA-155; quantified by real-time polymerase chain reaction. The gene target prediction databases revealed pellino 1 as a putative gene target for microRNA-155. The over-expression based studies of microRNA-155 mimics, scrambles, inhibitors, and cy3 negative control demonstrated the role of PELI1 in the regulation of the non-canonical NF-κB pathway via TRAF3. The luciferase assay showed the regulation of NF-κB promoter via microRNA-155 in JEV infected microglial cells. The suppression of NF-κB in JEV infected microglial cells led to the reduced expression of IL-6 and TNF-α. JEV exploits cellular microRNA-155 to suppress the expression of PELI1 in human microglial cells as a part of their immune evasion strategy.



中文翻译:

日本脑炎病毒利用microRNA-155抑制人类小胶质细胞中的非经典NF-κB途径

日本脑炎病毒(JEV)是一种单链正链RNA病毒,属于黄病毒科家庭。JEV本质上是神经质的,占神经系统疾病,精神病后遗症和运动障碍的30%至50%,儿童或老年人口的病死率为20%至30%。JEV引起神经元丢失和小胶质细胞活化,从而导致神经炎症。微小RNA是分子开关,其在转录后调节基因表达。据报道,microRNA-155与中枢神经系统相关的病理相关,例如实验性自身免疫性脑炎,多发性硬化症和肌萎缩性侧索硬化症。在本研究中,我们用JEV感染了小胶质细胞,从而导致microRNA-155的上调。通过实时聚合酶链反应定量。基因靶标预测数据库显示,pellino 1是microRNA-155的假定基因靶标。基于过表达的microRNA-155模拟物,加扰,抑制剂和cy3阴性对照研究表明,PELI1在通过TRAF3调节非经典NF-κB途径中发挥了作用。萤光素酶检测显示JEV感染的小胶质细胞中通过microRNA-155调节NF-κB启动子。JEV感染的小胶质细胞中NF-κB的抑制导致IL-6和TNF-α的表达降低。JEV利用细胞microRNA-155抑制HIF的表达 JEV感染的小胶质细胞中NF-κB的抑制导致IL-6和TNF-α的表达降低。JEV利用细胞microRNA-155抑制HIF的表达 JEV感染的小胶质细胞中NF-κB的抑制导致IL-6和TNF-α的表达降低。JEV利用细胞microRNA-155抑制HIF的表达人类小胶质细胞中的PELI1是其免疫逃避策略的一部分。

更新日期:2020-10-06
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