Li Yunchuan, Zhang Hao, Zhu Bibo, Ashraf Usama, Chen Zheng, Xu Qiuping, Zhou Dengyuan, Zheng Bohan, Song Yunfeng, Chen Huanchun, Ye Jing, Cao Shengbo
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.
Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Front Immunol. 2017 Sep 29;8:1237. doi: 10.3389/fimmu.2017.01237. eCollection 2017.
Japanese encephalitis virus (JEV) is the leading cause of epidemic encephalitis worldwide. JEV-induced neuroinflammation is characterized by profound neuronal cells damage accompanied by activation of glial cells. Albeit long non-coding RNAs (lncRNAs) have been emerged as important regulatory RNAs with profound effects on various biological processes, it is unknown how lncRNAs regulate JEV-induced inflammation. Here, using microarray approach, we identified 618 lncRNAs and 1,007 mRNAs differentially expressed in JEV-infected mice brain. The functional annotation analysis revealed that differentially regulated transcripts were predominantly involved in various signaling pathways related to host immune and inflammatory responses. The lncRNAs with their potential to regulate JEV-induced inflammatory response were identified by constructing the lncRNA-mRNA coexpression network. Furthermore, silencing of the two selected lncRNAs (E52329 and N54010) resulted in reducing the phosphorylation of JNK and MKK4, which are known to be involved during inflammatory response. Collectively, we first demonstrated the transcriptomic landscape of lncRNAs in mice brain infected with JEV and analyzed the coexpression network of differentially regulated lncRNAs and mRNAs during JEV infection. Our results provide a better understanding of the host response to JEV infection and suggest that the identified lncRNAs may be used as potential therapeutic targets for the management of Japanese encephalitis.
日本脑炎病毒(JEV)是全球流行性脑炎的主要病因。JEV诱导的神经炎症的特征是神经元细胞严重受损并伴有胶质细胞激活。尽管长链非编码RNA(lncRNA)已成为对各种生物过程具有深远影响的重要调节RNA,但尚不清楚lncRNA如何调节JEV诱导的炎症。在这里,我们使用微阵列方法,鉴定了在JEV感染的小鼠大脑中差异表达的618个lncRNA和1007个mRNA。功能注释分析表明,差异调节的转录本主要参与与宿主免疫和炎症反应相关的各种信号通路。通过构建lncRNA-mRNA共表达网络,鉴定了具有调节JEV诱导的炎症反应潜力的lncRNA。此外,沉默两个选定的lncRNA(E52329和N54010)导致JNK和MKK4的磷酸化减少,已知它们在炎症反应中起作用。总体而言,我们首次展示了JEV感染小鼠大脑中lncRNA的转录组图谱,并分析了JEV感染期间差异调节的lncRNA和mRNA的共表达网络。我们的结果有助于更好地理解宿主对JEV感染的反应,并表明所鉴定的lncRNA可能用作治疗日本脑炎的潜在治疗靶点。