Human respiratory epithelial cells acquire a long-lasting antiviral condition when exposed to interferon beta

Type I interferons (IFNs) induce strong antiviral effects and are therefore attractive to prevent seasonal respiratory infections or reduce the incidence of virus-mediated exacerbation in COPD patients. Yet, clinical application of type I IFNs is hindered due to significant side effects observed during repetitive use. In this study we investigate the duration of protection, mediated by prophylactic IFNbeta, against a human rhinovirus (HRV) infection. Human respiratory epithelial (A549) cells were exposed for 18 hours to various concentrations (31-500 IU/ml) of IFNbeta. Then, IFNbeta was either removed or maintained in the supernatant for the rest of the experiment. Next, cells were infected with HRV-1B (MOI 0.1) at t = 0, 24, 48, 72 or 168 hours after the initial exposure to IFNbeta. At 48 hours post infection, the protective effect of IFNbeta on HRV-induced cell death was determined by a colorimetric assay. RT-qPCR and plaque assay were used to determine HRV infection. In the continuous presence of IFNbeta, 90-100% of A549 cells were protected against HRV-induced cell death at every time point and at all IFNbeta concentrations. This strong protective effect was confirmed by RT-qPCR and plaque assay. Alternatively, when IFNbeta was removed, cell death increased with time and in dose-dependent way. Nevertheless, at 168h post IFNbeta stimulation (500IU/ml), still 75% of all cells were viable. These data show that IFNbeta has not only a strong, but also long-lasting protective effect against HRV-1B. This opens new opportunities for prophylactic treatment of viral respiratory infections without the risk of side effects often seen after repetitive and systemic use.