Detrimental role of type I interferon signaling in respiratory syncytial virus infection

摘要: Respiratory Syncytial Virus (RSV), the primary cause of lower respiratory tract infections in young children, is a poor inducer of type I interferons (IFN) and is resistant to its canonical antiviral activity. Paradoxically, increased type I IFN has been observed in some studies to correlate with more severe disease in RSV-infected children. Previously, we have shown that a pathogenic reactive oxygen species (ROS) production in the course of RSV infection is caused by a progressive reduction in nuclear and cellular levels of the transcription factor NF-E2-related factor 2 (NRF2), the primary regulator of antioxidant enzyme (AOE) gene expression. Thus, the goal of this study was to determine the contribution of type I IFN to lung innate/inflammatory responses, modulation of AOE expression, and airway disease in experimental RSV infection. Using either IFN alpha/beta receptor knockout mice or IFNAR neutralizing antibody …