RT Journal Article SR Electronic T1 Deficient production of IFN-stimulated genes upon rhinovirus infection in cystic fibrosis airway epithelial cells JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 363 VO 38 IS Suppl 55 A1 Elisabeth Kieninger A1 Marjolaine Vareille A1 Marco P. Alves A1 Brigitte S. Kopf A1 Thomas Geiser A1 Sebastian L. Johnston A1 Michael R. Edwards A1 Nicolas Regamey YR 2011 UL http://erj.ersjournals.com/content/38/Suppl_55/363.abstract AB Background: Rhinoviruses (RVs) are important triggers of pulmonary exacerbations and possible contributors to long-term respiratory morbidity in cystic fibrosis (CF), but mechanisms leading to RV-induced CF exacerbations are poorly understood. We recently described deficient innate immune responses to RV infection in CF characterized by impaired type I and III interferon (IFN) production and increased virus replication.To study downstream effects of impaired IFN induction we investigated the expression of IFN-stimulated genes (ISGs) which are important for the production of antiviral proteins.Methods: Epithelial CF and non-CF cell lines (UNCCF2T/UNCN2T, CFBE41o-/16HBE14o-) were cultured and infected with RV-16 and -1B at a MOI of 2. Induction of ISGs including MxA, 2',5'-OAS, viperin and NOS2 was assessed by RT-PCR. Exogenous IFN-β and -λ were added before and after infection.Results: Expression of all ISGs was induced in CF and control cells upon virus infection. CF cells expressed 100-1000 times less ISGs than control cells (all p<0.05). ISG expression and RV replication were inversely related (MxA: r=-0.79, p=0.001). There was a positive correlation between ISG expression and IFN-β (2',5'-OAS: r=0.74, p=0.004) and IFN-λ production (NOS2: r=0.65, p=0.01). Exogenous IFN increased levels of ISGs to the level of control cells, with a more pronounced effect of IFN-β.Conclusions: ISG induction upon RV infection is deficient in CF indicating a profound impairment of the early innate antiviral response. Addition of exogenous IFN restores antiviral pathways in CF, suggesting a potential use of IFNs in the prevention or treatment of RV-induced CF exacerbations.