Expression Profile and Function Analysis of Long Non-coding RNAs in the Infection of Coxsackievirus B3

The roles of lncRNAs in the infection of enteroviruses have been barely demonstrated. In this study, we used coxsackievirus B3 (CVB3), a typical enterovirus, as a model to investigate the expression profiles and functional roles of lncRNAs in enterovirus infection. We profiled lncRNAs and mRNA expression in CVB3-infected HeLa cells by lncRNA-mRNA integrated microarrays. As a result, 700 differentially expressed lncRNAs (431 up-regulated and 269 down-regulated) and 665 differentially expressed mRNAs (299 up-regulated and 366 down-regulated) were identified in CVB3 infection. Then we performed lncRNA-mRNA integrated pathway analysis to identify potential functional impacts of the differentially expressed mRNAs, in which lncRNA-mRNA correlation network was built. According to lncRNA-mRNA correlation, we found that XLOC-001188, an lncRNA down-regulated in CVB3 infection, was negatively correlated with NFAT5 mRNA, an anti-CVB3 gene reported previously. This interaction was supported by qPCR detection following siRNA-mediated knockdown of XLOC-001188, which showed an increase of NFAT5 mRNA and a reduction of CVB3 genomic RNA. In addition, we observed that four most significantly altered lncRNAs, SNHG11, RP11-145F16.2, RP11-1023L17.1 and RP11-1021N1.2 share several common correlated genes critical for CVB3 infection, such as BRE and IRF2BP1. In all, our studies reveal the alteration of lncRNA expression in CVB3 infection and its potential influence on CVB3 replication, providing useful information for future studies of enterovirus infection.