OBJECTIVE: As an extracellular vesicle, exosomes can release from virus-infected cells containing various viral or host cellular elements and could stimulate recipient's cellular response. Enterovirus 71 (EV71), a single-strand positive-sense RNA virus, is known to cause hand, foot, and mouth disease (HFMD) in children and bring about severe clinical diseases.METHODS: Separated the human oral epithelial cells (OE cells) from normal buccal mucosa through enzyme digestion. Performed a comprehensive miRNA profiling in exosomes from EV71-infected OE cells through deep small RNA-seq. Using the Human Antiviral Response RT Profiler PCR Array profiles to explore the interactions of innate immune signaling networks with exosomal miR-30a. Knocked out the MyD88 gene in macrophages using CRISPR/Cas9-mediated genome editing method.RESULTS: Our study demonstrated that the miR-30a was preferentially enriched in exosomes that released from EV71-infected human oral epithelial cells through small RNA-seq. We found that the transfer of exosomal miR-30a to macrophages could suppress type ? interferon response through targeting myeloid differentiation factor 88 (MyD88) and subsequently facilitate the viral replication.CONCLUSIONS: Exosomes released from EV71-infected OE cells selectively packaged high level of miR-30a that can be functionally transferred to the recipient macrophages resulted in targeting MyD88 and subsequently inhibited type I interferon production in receipt cells, thus promoting the EV71 replication.
Cells, Cultured Enterovirus A, Human