The Role of ROS in RSV Induced Lung Pathogenesis

University Of Texas Medical Br Galveston, Galveston TX

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Abstract

DESCRIPTION (provided by applicant): Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract illness in infants and young children worldwide. In addition, long-term morbidity associated with severe RSV infections in early life may include developing asthma or recurrent wheezing. The mechanisms of RSV-induced airway disease are not fully understood, but pulmonary inflammation is thought to play a key role in the pathogenesis of this condition. We have shown that RSV-induced inflammation is mediated in part by the expression of redox-sensitive chemokines. In this project we will pursue the hypothesis that reactive oxygen species (ROS) play an important role in the pathogenesis of RSV-induced lung disease. In vitro and experimental mouse models of RSV infection in combination with antioxidant treatment will be employed to determine whether RSV- generated oxidative response is involved in transcription factor activation and chemokine gene expression, to further characterize RSV-induced oxidative stress responses, and to identify whether ROS contribute to the overall progression of pulmonary inflammation and clinical disease. Relevant to new treatment approaches, we aim to determine whether an enhanced antioxidant capacity may attenuate viral-induced airway disease.