MicroRNA expression profile of human umbilical vein endothelial cells in response to coxsackievirus A10 infection reveals a potential role of miR-143-3p in maintaining the integrity of the blood–brain barrier

Abstract

Coxsackievirus A10 (CV-A10) has been one of the main etiologies of hand, foot, and mouth disease (HFMD) epidemics in recent years and can cause mild to severe illness and even death. Most of these severe and fatal cases were closely associated with neurological impairments, but the potential mechanism of neuropathological injury triggered by CV-A10 infection has not been elucidated. MicroRNAs (miRNAs), implicated in the regulation of gene expression in a post-transcriptional manner, play a vital role in the pathogenesis of various central nervous system (CNS) diseases; therefore, they serve as diagnostic biomarkers and are emerging as novel therapeutic targets for CNS injuries. To gain insights into the CV-A10-induced regulation of host miRNA-processing machinery, we employed high-throughput sequencing to identify differentially expressed miRNAs in CV-A10-infected human umbilical vein endothelial cells (HUVECs) and further analyzed the potential functions of these miRNAs during CV-A10 infection. The results showed that CV-A10 infection could induce 189 and 302 significantly differentially expressed miRNAs in HUVECs at 24 and 72 hpi, respectively, compared with the uninfected control. Moreover, the expression of four selected miRNAs and their relevant mRNAs was determined to verify the sequencing data by quantitative reverse transcription–polymerase chain reaction (RT–qPCR) methods. After that, gene target prediction and functional annotation revealed that the targets of these dysregulated miRNAs were mostly enriched in cell proliferation, signal transduction, cAMP signalling pathway, cellular response to interleukin-6, ventral spinal cord interneuron differentiation, negative regulation of glial cell differentiation, neuron migration, positive regulation of neuron projection development, etc., which were primarily involved in the processes of basic physiology, host immunity, and neurological impairments and further reflected vital regulatory roles of miRNA in viral pathogenicity. Finally, the construction of a miRNA-regulated network also suggested that the complex regulatory mechanisms mediated by miRNAs might be involved in viral pathogenesis and virus–host interactions during CV-A10 infection. Furthermore, among these dysregulated miRNAs, miR-143-3p was demonstrated to be involved in the maintenance of blood–brain barrier (BBB) integrity.

Varicella‐zoster virus‐related neurological complications: From infection to immunomodulatory therapies

“…divides the brain and spinal cord from the circulation. 88 While both viruses may infect and cross the human BBB, the outcomes of their The study also demonstrated that the exogenous hedgehog agonist S-Adenosyl-L-homocysteine can protect against meningitic E. colicaused BBB dysfunction. 90 Deterioration of the BBB is complex, including direct Human Immunodeficiency Virus infection of neurovascular unit cells, particularly pericytes and perivascular macrophages, as well as the release of pro-inflammatory cytokines and viral proteins from infected cells.…”

“…91 According to research, coxsackievirus A10 (CV-A10) infection may cause differences in the way that microRNAs are expressed in human umbilical vein endothelial cells, which are essential for preserving the integrity of the BBB. 88…”

Research progress on the mechanism of exosome-mediated virus infection

“…The exosomes of EV71-infected RMS cells contain EV71 RNA, viral capsid protein VP1 and EV71 particles, which, partially resistant to antibody neutralization, can establish an effective infection in vitro ( Gu et al., 2020 ). However, exosomes of human oral epithelial cells infected with EV71 selectively package high levels of miR-30a, which can be delivered to macrophages and inhibit the type I IFN response by targeting the bone marrow differentiation factor 88 (MyD88), thereby enhancing viral replication ( Hu et al., 2023 ). It can induce the increase of exosomes secreted by colon cancer cell line HT29 and human mononuclear/macrophage cell line THP-1, meanwhile the EV71 virus nucleic acid carried in those exosomes can break through the limitation of virus-specific receptors and assemble its own genes into exosomes to expand the range of host infection ( Li et al., 2019 ).…”