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Kyyaly, A.

Publications and source records attributed to Kyyaly, A..

2 recordsLinked to original sources

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

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.

microbiology↗

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.

microbiology↗