Human rhinovirus 16 infection of Hela-Ohio and HEp-2 cells modifies micro RNA expression across the viral life-cycle

Abstract

Human rhinovirus (RV) is the most frequent cause of the common cold, as well as severe exacerbations of chronic obstructive pulmonary disease (COPD) and asthma. Currently, there are no effective and accurate diagnostic tools or antiviral therapies. MicroRNAs (miRNAs) are small, non-coding sections of RNA involved in the regulation of gene expression and have been shown to be associated with different pathologies. However, the precise role of miRNAs in RV infection is not yet well established. This study aimed to analyse the impact of RV16 on miRNA expression across the viral life-cycle to identify a small panel with altered expression. We then aimed to specifically interrogate these results using our in-house developed modelling programme to identify specific genes regulated by these miRNAs during RV infection which can then be tested functionally. Our results first identified that three miRNAs, miR-155-5p, miR-140-3p, and miR-122-5p were potential biomarkers being differentially regulated at specific time points post infection. Our modelling program then linked these miRNAs to four genes (OLFML3, STAG2, SMARCA2, CD40LG) that play important roles in regulating the hosts antiviral responses and viral progression. Together, this work identifies a potential panel of biomarkers that could, along with our previous work, form clear diagnostic markers for RV16 infection and identifies specific targets that can be functionally interrogated helping to identify new cellular targets modified by RV16 infection that could inform future therapeutic design.