Inhibition of Pim1 kinase reduces viral replication in primary bronchial epithelial cells

Respiratory viral infections are responsible for 85% of asthma exacerbations, which in turn lead to increased morbidity and mortality, causing a high societal and economic burden [1, 2]. Asthma patients have been found to be more susceptible to viral infections compared with non-asthmatic individuals [3]. It has been postulated that a reduced induction of apoptosis in virally infected airway epithelial cells from asthmatic patients might play a role in this increased susceptibility to viral infections [4]. Building on the role of apoptosis in respiratory viral infections, we tested whether the inhibition of a well-known survival pathway active in airway epithelial cells could reduce viral replication. To this end, we used an in vitro approach and infected primary bronchial epithelial cells (PBECs) from healthy volunteers with human rhinovirus (HRV)-16 in the absence or presence of a highly specific pharmacological inhibitor for Pim1 kinase [5]. Pim1 kinase is a constitutively active serine/threonine kinase known to be involved in cell survival by increasing the threshold for apoptosis [6, 7]. We have shown previously that Pim1 kinase is highly expressed in the bronchial airway epithelium and that pharmacological inhibition of Pim1 kinase increases the sensitivity of bronchial epithelial cells to cell death upon challenge with cigarette smoke extract [8]. Therefore, we hypothesised that inhibition of Pim1 kinase activity in virally infected PBECs would enhance the onset of cell death, resulting in reduced viral replication. Inhibition of Pim1 kinase activity reduces viral replication by inducing the onset of bronchial epithelial cell death The authors would like to thank Juerg Schwaller (University Children's Hospital of Basel, Basel, Switzerland) and Andrew Kraft (Medical University of South Carolina, Charleston, SC, USA) for providing the Pim1 inhibitors K00135 and SMI-4a, respectively, and Robert Ridley and Graham Berreen (University Hospital Southampton, Southampton, UK) for the technical assistance with the primary bronchial epithelial cell cultures.