Microarray analysis of lncRNA expression in rabies virus infected human neuroblastoma cells

Rabies, caused by the rabies virus (RABV), is the oldest known zoonotic infectious disease. Although the molecular mechanisms of RABV pathogenesis have been investigated extensively, the interactions between host and RABV are not clearly understood. It is now known that long non-coding RNAs (lncRNAs) participate in various physiological and pathological processes, but their possible roles in the host response to RABV infection remain to be elucidated. To better understand the pathogenesis of RABV, RNAs from RABV-infected and uninfected human neuroblastoma cells (SK-N-SH) were analyzed using human lncRNA microarrays. We identified 896 lncRNAs and 579 mRNAs that were differentially expressed after infection, indicating a potential role for lncRNAs in the immune response to RABV. Differentially expressed RNAs were examined using Gene Ontology (GO) analysis and were tentatively assigned to biological pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG). A lncRNA -mRNA-transcription factor co-expression network was constructed to relate lncRNAs to regulatory factors and pathways that may be important in virus-host interactions. The network analysis suggests that E2F4, TAF7 and several lncRNAs function as transcriptional regulators in various signaling pathways. This study is the first global analysis of lncRNA and mRNA co-expression during RABV infection, provides deeper insight into the mechanism of RABV pathogenesis, and reveals promising candidate for future investigation.

由狂犬病病毒（RABV）引起的狂犬病是已知最古老的人畜共患传染病。尽管狂犬病病毒致病的分子机制已被广泛研究，但宿主与狂犬病病毒之间的相互作用仍未被清晰了解。现在已知长链非编码RNA（lncRNAs）参与各种生理和病理过程，但它们在宿主对狂犬病病毒感染的反应中可能发挥的作用仍有待阐明。为了更好地理解狂犬病病毒的致病机制，使用人lncRNA微阵列分析了来自狂犬病病毒感染和未感染的人神经母细胞瘤细胞（SK - N - SH）的RNA。我们鉴定出896种lncRNAs和579种mRNA在感染后差异表达，这表明lncRNAs在对狂犬病病毒的免疫反应中具有潜在作用。使用基因本体论（GO）分析对差异表达的RNA进行了检测，并使用京都基因与基因组百科全书（KEGG）初步将它们归类到生物学通路中。构建了一个lncRNA - mRNA -转录因子共表达网络，将lncRNAs与在病毒 - 宿主相互作用中可能很重要的调节因子和通路联系起来。网络分析表明，E2F4、TAF7和几种lncRNAs在各种信号通路中作为转录调节因子发挥作用。这项研究是对狂犬病病毒感染期间lncRNA和mRNA共表达的首次全面分析，为狂犬病病毒致病机制提供了更深入的见解，并揭示了未来研究有希望的候选对象。