Positive Feedback Loop of Long Noncoding RNA OASL-IT1 and Innate Immune Response Restricts the Replication of Zika Virus in Epithelial A549 Cells
Positive Feedback Loop of Long Noncoding RNA OASL-IT1 and Innate Immune Response Restricts the Replication of Zika Virus in Epithelial A549 Cells
复制标题
DOI：
10.1159/000513606
复制
发表时间：
2021-02
影响因子：
5.3
通讯作者：
Yi Wang;Zhiting Huo;Quanshi Lin;Yuxia Lin;Cancan Chen;Yanxia Huang;Changbai Huang;Junsong Zhang;Junfang He;Chao Liu;Ping Zhang
中科院分区：
文献类型：
--
作者：
Yi Wang;Zhiting Huo;Quanshi Lin;Yuxia Lin;Cancan Chen;Yanxia Huang;Changbai Huang;Junsong Zhang;Junfang He;Chao Liu;Ping Zhang
病毒感染显著改变宿主非编码rna和编码mrna的表达。在本研究中，我们采用芯片技术筛选了感染寨卡病毒（ZIKV）的人肺上皮A549细胞的转录谱。79个长链非编码rna （lncRNAs）和140个mrna差异表达（DE）。生物信息学分析显示，与DE lncrna相邻的mrna与宿主对病毒感染的反应密切相关。我们从前50个点击率中选择了7个lncrna进行验证。实时荧光定量PCR数据证实，所选lncRNAs的表达是由ZIKV感染诱导的。此外，7个lncRNAs的表达可被登革热病毒、日本脑炎病毒、水疱性口炎病毒感染或poly（I:C）和IFN-β诱导。此外，先天免疫接头IPS-1或受体IFNAR1的缺失导致ZIKV诱导几种lncrna的水平降低。3个lncRNAs （RPL27-OT1、OASL-IT1和REC8-OT3）的过表达降低了ZIKV病毒的产量。敲除OASL-IT1显著增强ZIKV复制。在OASL-IT1敲除细胞中，干扰素（ifn）水平和ZIKV触发的3种先天免疫信号通路的激活显著降低。总的来说，我们的工作发现IFN系统中存在一个正反馈回路，IFN和OASL-IT1相互调节，从而促进抗病毒防御的建立。
Expression of host noncoding RNAs and coding mRNAs is significantly altered by viral infection. In the current study, we screened the transcriptional profile of human lung epithelial A549 cells infected with Zika virus (ZIKV) by microarray assay. Seventy-nine long noncoding RNAs (lncRNAs) and 140 mRNAs were differentially expressed (DE). The bioinformatics analysis revealed that the mRNAs adjacent to the DE lncRNAs were closely related to the host responses to viral infection. We selected 7 lncRNAs from the top 50 hits for validation. The quantitative real-time PCR data confirmed that expression of selected lncRNAs was induced by ZIKV infection. Moreover, the expression of 7 lncRNAs was induced by infection of dengue virus, Japanese encephalitis virus, or vesicular stomatitis virus, or by treatment of poly(I:C) and IFN-β. Furthermore, loss of innate immune adaptor IPS-1 or receptor IFNAR1 resulted in lower induction levels of several lncRNAs by ZIKV. Overexpression of 3 lncRNAs (RPL27-OT1, OASL-IT1, and REC8-OT3) reduced the virus yields of ZIKV. Knockout of OASL-IT1 significantly enhanced ZIKV replication. In OASL-IT1 knockout cells, the levels of interferons (IFNs) and the activation of 3 innate immune signaling pathways triggered by ZIKV were dramatically reduced. Collectively, our work found a positive feedback loop in the IFN system, in which IFNs and OASL-IT1 regulate each other, thereby promoting establishment of antiviral defense.