Screening the Action Targets of Enterovirus 71 in Human SH-SY5Y Cells Using RNA Sequencing Data

Abstract

Hand, foot, and mouth disease (HFMD) is a common infection for children younger than the age of five. HFMD is mainly induced by coxsackievirus A16 and enterovirus 71 (EV71). EV71-associated HFMD often has serious neurological disease complications. The purpose of this study was to reveal the mechanisms of action of EV71 on neurons. SH-SY5Y cells transfected or untransfected with EV71 were sequenced. After data preprocessing, differentially expressed genes (DEGs) were screened using the limma package in R, and clustering analysis was then performed using the ComplexHeatmap package in R. The DAVID tool was used for EDG enrichment analysis. Protein-protein interactions (PPIs) were predicted using the STRING database and PPI networks were then constructed using Cytoscape software. After pathways involved in the key PPI network nodes were enriched, pathway deviation scores were calculated. Clustering analysis was also conducted for these pathways. There were 978 DEGs in the transfected samples. Upregulated TNF was enriched in NF-kappa B signaling pathway. Among the top 20 nodes in the PPI network, CDK1, STAT3, CCND1, TNF, and MYC had the highest degrees. A total of 28 pathways were enriched for the top 20 nodes, including Epstein-Barr virus infection (p = 3.78E-06), proteoglycans in cancer (p = 4.96E-06), and melanoma (p = 1.99E-05). In addition, clustering analysis showed that these pathways could clearly differentiate the two groups of samples. EV71 may affect neurons by mediating CDK1, STAT3, CCND1, TNF, and MYC, indicating that these genes are promising targets for preventing the neuronal complications of HFMD.