Exacerbations cause major morbidity and significant mortality in asthma. Respiratory viral infections account for up to 85% of exacerbations with human Rhinovorus (RV) of the greatest preponderance. In order to replicate within host cells, RV hijacks the translational machinery of the cell, the endoplasmic reticulum (ER). This increase in protein production overwhelms the folding and secretory capacity of the ER causing ER stress. In order to ameliorate these harmful processes, the cell engages the unfolded protein response (UPR). The UPR signalling pathway governs cell fate, either to promote protein folding and restore protein homeostasis or activate apoptosis. ER stress has previously been implicated in viral infection and asthma alone however, the role of respiratory viral-induced ER stress in asthma exacerbations remains to be fully elucidated. With this is mind, my project aims to define the ability of RV to induce ER stress in primary airway epithelial cells from both healthy and asthmatic donors and assess whether this may provide a target for therapeutic intervention. |
The Team
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