An animal model of enhanced disease development following respiratory viral infection in children with chronic lung diseases

Abstract

Abstract Infants born prematurely often develop chronic lung diseases including bronchopulmonary dysplasia (BPD). BPD is associated with greatly increased host susceptibility and severe disease development following respiratory viral infection. To this end, we have recently established a neonatal hyperoxia model respiratory viral infection in hosts with lung prematurity and BPD. Using this model, we observed that mice exposed with neonatal hyperoxia (80% oxygen, BPD hosts) developed enhanced diseases following influenza virus or respiratory syncytial virus (RSV) infection compared to those of influenza or RSV-infected control mice. We showed that neonatal hyperoxia leaded to modestly enhanced viral replication in the respiratory tract. Using nanostring immune gene profiling and multiplex cytokine analysis, we found that neonatal hyperoxia markedly enhanced immune-associated gene expression and the production of a number of proinflammatory cytokines and chemokines in the airway compared to those of control mice. Neonatal hyperoxia also increased the accumulation of multiple inflammatory innate cell types that were shown to be pathogenic during respiratory viral infections. Importantly, antiviral T, B cells and NK cells were similar in the lungs between infected neonatal hyperoxia-exposed and control mice, which are consistent with the similar viral clearance kinetics in those mice. Thus, we have successfully established a clinically-relevant mouse model of respiratory viral infection in BPD hosts. We expect to further uncover novel insights on the viral pathogenesis and host disease devlopment in this novel model of respiratory viral infection in hosts with chronic lung diseases.