GSE133634
Comprehensive analyses of function and molecular interaction of differential expressed non-coding RNAs and mRNA in Hantaan virus infection
Hantaan virus (HTNV), the prevalent prototype of the hantavirus in Asia, causes hemorrhagic fever with renal syndrome (HFRS) with high mortality in human being. However, the pathogenesis of HTNV infection remains elusive. Accumulating evidences indicate that non-coding RNAs (ncRNAs), including long non-coding RNA (lncRNA), circular RNA (circRNA) and microRNA (miRNA) play crucial roles in the progression of virus infection. Here, we identified differential lncRNA/miRNA/circRNA and mRNA expression profiles of HTNV-infected  human umbilical vein endothelial cells (HUVECs) compared with mock-infected HUVECs by whole transcriptome sequencing. Subsequently, comprehensive bioinformatics analyses established miRNA-mRNA co-expression, protein-protein interaction and competing endogenous RNA (ceRNA) networks in miRNA-lncRNA-circRNA-mRNA regulatory axis. The trans or cis regulatory roles of identified RNAs on HTNV infection were ascertained by RNA interference and key ceRNA relationships were verified by dual-luciferase reporter experiments. Moreover, gene ontology (GO) enrichment analysis showed that dysregulated RNAs were mostly related to antiviral innate immune response. In conclusion, our findings firstly revealed that circRNAs and ceRNA network were involved in regulating HTNV infection, and also confirmed several key lncRNAs and miRNAs which had vital effects on HTNV infection. The identification and characterization of RNAs provide the new insights on ceRNA networks in HTNV-host interactions, which lays the foundation for future research of the potential roles of ncRNAs in the pathogenesis of HFRS. Overall design: Mock-infected and Hantaan virus-infected HUVECs were generated by deep sequencing, in triplicate respectively