Research Project
10270981
Summary: Respiratory syncytial virus (RSV) is the leading viral agent causing bronchiolitis and pneumonia in children under five years and RSV bronchiolitis often develop recurrent wheezing and asthma during childhood. It remains unanswered whether RSV infection confers a long-term change in the host, which increases the subsequent risk of asthma. We have optimized a system of pseudostratified, highly differentiated respiratory epithelium by culturing primary normal human bronchial epithelial (NHBE) cells in an air-liquid interface (ALI) culture to study how RSV infection increases the risk of asthma. Our preliminary data showed RSV infection of the cultures increased actin-cytoskeleton, resulted in an expanded infected-cell perimeter. Additionally, we found that many genes involved in epigenetic regulation of transcription were modulated during RSV infection. Our central goal of this project is to investigate whether RSV-induced epigenetic changes contribute to asthma progression. We will determine cell-specific epigenetic changes in the RSV-infected respiratory epithelium by identify both intrinsic (cellular) and extrinsic (viral) factors contributing to asthma progression. We will also determine how RSV proteins expression alters cellular transcription, splicing, and chromatin structure by comparing gene expression, RNA splicing and chromatin accessibility. The results of the proposed studies will establish a novel viral-induced epigenetic changes as an extrinsic factor and identify potential epigenetic predictors of chronic lung diseases. This will eventually help to identify novel interventions against RSV and RSV-dependent risk of asthma progression.
