ENAGenomicsThe Second Affiliated Hospital of Xi'an Jiaotong Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA1299456Enterovirus A71Objective Enterovirus 71 (EV-A71) is a major pathogen of severe hand, foot and mouth disease (HFMD) in children, but the mechanism by which it develops into severe HFMD remains unclear, especially the role of macrophage-mediated immune dysregulation. Methods Macrophages infected with EV-A71 were collected for transcriptomic analysis, and were indirectly co-cultured with nerve cells to observe their inhibitory effects on nerve cells. Results High concentration of EV-A71 infected macrophage supernatant inhibited SH-SY5Y cell proliferation. ENSG00000285779, TICAM2, RPL13AP26 and HNF4G are significantly different in EV-A71 or inactivated EV-A71 infected macrophages than in control. ENSG00000264324, ENSG00000260643, ISLR2, CCR7, TENM4, INO80B-WBP1, BLOC1S5-TXNDC5 are potential genes about direct virus damage or viral RNA recognition in macrophages. GO annotation and KEGG analysis indicate that EV-A71 infection cause the changes of neural receptor-ligand binding pathway, activation of specific immunity, calcium signaling pathway, and cell aggregation. Conclusions Macrophages are activated early during EV-A71 infection, thus initiating specific immunity, which is closely related to the severe HFMD. The nerve damage pathway and calcium signaling pathway caused by EV-A71 virus infection of macrophages deserve to more attention. Overall design: THP-1 cell-induced macrophages infected with EV-A71, inactivated EV-A71 were collected for transcriptomic analysis,and THP-1 cell-induced macrophages were control group.pathogen:prioritypathogenpathogen:virusENAvirusesfalseTranscriptomic Analysis Initially Reveals Monocyte/Macrophage Activation Drives EV-A71-Induced Immune Dysregulation and Neural Injury in Severe HFMDTranscriptomic Analysis Initially Reveals Monocyte/Macrophage Activation Drives EV-A71-Induced Immune Dysregulation and Neural Injury in Severe HFMD2025-09-162025-09-16PRJNA1299456GSE30423939054