Human rhinovirus 16 infection modifies the microRNA landscape during epithelial cell infection.

Human rhinovirus is a major driver of disease exacerbations for patients with asthma and chronic obstructive pulmonary disease. Importantly, the virus can disrupt immune cell functioning leading to secondary bacterial infections in these patients. MicroRNAs are important regulators of gene expression and control viral pathogenesis and immune cell functions. However, the role of different miRNAs during rhinovirus infections remains poorly defined. The aim of this study was to analyze the impact of RV16 on epithelial cell responses and identify miRNAs with altered expression levels in response to the viral infection and their target genes. HeLa-Ohio cells exposed to RV16 showed deficiencies in bacterial clearance and induced changes in the expression of several novel miRNAs identified using a custom panel of 88 different miRNAs and further analyzed using our newly developed computer program. Our experiments identified a panel of 9 differentially regulated miRNAs and our computer program narrowed this down to two that could represent biomarkers for RV16 infection. Our results also showed that upon upregulation of these miRNAs (miR-101-3p and miR-30b-5p) by RV16 there was a downregulation in EZH2, RARG and PTPN13 that could correlate with a productive viral infection and a worsened immune response. Taken together, our findings suggest that RV16 modifies the miRNA landscape in epithelial cells and that miR-101-3p and miR-30b-5p could represent key biomarkers for either early or late RV16 infection.