Characterization of Long Non-coding RNA Profile in RD and SH-SY5Y Cells Infected by CV-B5 using RNA Sequencing

Abstract

Hand, foot, and mouth disease caused by Coxsackievirus B5 (CV-B5) poses considerable threats to the health of infants especially in neurological damage. And the long noncoding RNAs (lncRNAs) act pivotal factors in regulating and participating in virus-host interactions. However, the role of lncRNAs in CV-B5-host interactions has not yet been elucidated. In this study, we used the RNA sequencing to determine the expression profiles of lncRNAs in CV-B5 infected human rhabdomyosarcoma (RD) and SH-SY5Y cells. Our results identified that in the differentially expressed lncRNAs a total of 508 up-regulated and 760 down-regulated lncRNAs in RD cell, with 46.2% were lincRNAs, 28.6% were anti-sense lncRNAs, 24.1% were sense overlapping lncRNAs, and 1.0% were sense intronic lncRNAs. Moreover, 792 lncRNAs were significantly increased and 811 lncRNAs were greatly decreased in SH-SY5Y cell including 48.6% were lincRNAs, 34.7% were anti-sense lncRNAs, 16.0% were sense overlapping lncRNAs, and 0.8% were sense intronic lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed that the differentially expressed lncRNAs participated in the occurrence of disease in RD cell and associated with signaling pathway in SH-SY5Y cell after CVB5 infection respectively. In addition, similar results were obtained when seven lncRNAs were selected for validation using RT-qPCR assays. Moreover, we conducted the candidate lncRNA-IL12A secondary structures and found that it inhibits viral replication through Wnt signaling pathway. Our results reveal that lncRNAs can become a possible novel molecular target for the prevention and treatment of CV-B5 infection, and provided information for distinguishing neurogenic CV-B5 disease.