Inhibition of Pim1 kinase augments the anti-viral response to rhinovirus infection

Asthma is a chronic inflammatory disease characterized by reversible airflow obstruction and bronchial hyperreactivity. Asthmatic patients frequently suffer from exacerbations, mainly triggered by viral infections, and therapeutic options are limited. The anti-viral response in asthmatic patients is compromised and factors augmenting this response could offer new therapeutic approaches. Here, we hypothesized that Pim1 kinase, known to stabilize SOCS-proteins that interfere with interferon signalling, could be such a new therapeutic target. Air-liquid interface (ALI) cultures of primary bronchial epithelial cells (PBEC) were exposed to rhinovirus (RV16) without or with pharmacological inhibition of Pim1 kinase. Viral replication and viral load were measured by qPCR and HeLa cell titration assay. Anti-viral responses were measured by analysing IFN-β, IL-29, IP-10 and RANTES expression. Protein levels of SOCS-3 and p-STAT1 were determined by Western Blotting. Inhibition of Pim1 kinase significantly reduced viral replication in ALI cultures of healthy volunteers, which was accompanied by an increase in anti-viral responses 12 hours after RV16 infection. Although no difference in SOCS-3 levels were detectable, STAT1 phosphorylation was higher in RV16-infected PBECs when Pim1 kinase activity was inhibited. A comparable reduction in viral infection and increase in anti-viral responses was observed in ALI cultures of severe asthmatics. In conclusion, our data suggest that Pim1 kinase facilitates viral replication by suppressing anti-viral signalling. The therapeutic potential of Pim1 kinase inhibition for treatment of viral-induced asthma exacerbations should be further explored.