Respiratory Syncytial Virus Infection Induces Airway Hyperresponsiveness Through miR-34b/c-5p/CXCL10 Axis

Abstract Background: There is growing evidence on miRNAs with pivotal role in viral infection-induced airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). However, the related mechanism of RSV infection affecting airway inflammation and airway hyperresponsiveness (AHR) is largely unknown.Methods：We obtained the miRNA and mRNA databases of patients with RSV infection, as well as the miRNA databases of asthma and COPD patients from the GEO database. Through intergrated analysis we screened differentially expressed miRNAs (DEmiRs) and genes (DEGs).Further analysis was carried out to obtain the hub gene through the biological pathways and enrichment pathways of DEGs targeted by DEmiRs and construction of a protein-protein interaction (PPI) network. Finally, the expression of DEmiRs and hub gene were verified in vivo and in vitro experiments, and the regulatory relationship between DEmiRs and hub gene was further explored.Results: The five differential molecules (miR-34b/c-5p, CD14, CXCL10 and RHOH) screened through animal experiments have the same expression trend in the acute and chronic phases of RSV infection. Following the infecting of BEAS-2B cells with RSV, we confirmed that RSV infection can down-regulate miR-34b/c-5p, and the expression levels of CXCL10 and CD14 were significantly increased in the infected group. Furthermore, the results of the dual-luciferase reporter assay showed that CXCL10 is the target of miR-34c-5p.Conclusion: We confirmed that the increase of CXCL10 after RSV infection is regulated by miR-34b/c-5p. This study shed some lights on the mechanism of RSV infection affecting airway inflammation and AHR. In addition, the study provides diagnostic indicators and therapeutic targets for AHR caused by persistent RSV infection.