BackgroundRespiratory syncytial virus (RSV) is the main pathogen causing acute bronchiolitis, which is common in infants and young children. A previous study revealed the possible involvement of POU class 2 associating factor 1 (POU2AF1) in RSV-triggered acute bronchiolitis. We attempted to clarify the specific action mechanism of POU2AF1 underlying RSV-triggered inflammation.MethodsRT-qPCR measured POU2AF1 levels in RSV-infected children, mice, and airway epithelial cell lines (HBECs). HE staining showed histopathological features in the lung tissue of RSV-infected mice. ELISA examined the contents of proinflammatory cytokines in RSV-infected mice. Western blotting evaluated the protein abundance of proinflammatory cytokines in RSV-infected HBECs and assessed NF-κB pathway-associated protein expression in RSV-infected mice and RSV-treated HBECs.ResultsPOU2AF1 presented depletion in RSV-infected children, mice, and HBECs. RSV-infected triggered lung injury and inflammatory cell infiltration in the mouse lung tissue, while POU2AF1 overexpression rescued these changes. RSV-infected induced inflammatory impairment in HBECs, whereas POU2AF1 reversed this effect. POU2AF1 suppressed the upregulated NF-κB pathway-associated protein expression in mice and HBECs under RSV infection.ConclusionPOU2AF1 exerts a protective impact on RSV-induced acute bronchiolitis in vitro and in vivo through the NF-κB pathway. Our research may provide a novel direction for better therapy of RSV-triggered acute bronchiolitis.