Transcriptome of human neuroblastoma SH-SY5Y cells in response to 2B protein of enterovirus-A71.

Infection with enterovirus-A71 (EV-A71) can cause hand-foot-mouth disease associated with fatal neurological complications. The host response to EV-A71 has not yet been fully elucidated, thus, hampering the development of a precise therapeutic approach. A nonstructural 2B protein of EV-A71 has been reported to involve with calcium dysregulation and apoptosis induction in human neuroblastoma SH-SY5Y cells. However, the molecular mechanism has not been delineated. To address this, comprehensive study of the gene expression from SH-SY5Y cells transfected with EV-A71 2B was carried out by RNA sequencing and transcriptomic analysis. It was found that the signature of the upregulated genes of SH-SY5Y cells expressing EV-A71 2B involved the Ca2+-related signaling pathways participating gene expression, inflammatory response, apoptosis, and long-term potentiation of the neuron. Protein-protein interaction network analysis revealed that the products encoded by CCL2, RELB, BIRC3, and TNFRSF9 were the most significant hub proteins in the network. It indicated that EV-A71 2B protein might play a role in immunopathogenesis of the central nervous system (CNS) which probably associated with the non-canonical NF-κB pathway. The data suggest that transcriptomic profiling can provide novel information source for studying the neuropathogenesis of EV-A71 infection leading to development of an effective therapeutic measure for CNS complications.