RSV-induced Expanded Ciliated Cells Contribute to Bronchial Wall Thickening

Talukdar, S. N.; Osan, J.; Ryan, K.; Grove, B.; Perley, D.; Kumar, B. D.; Yang, S.; Dallman, S.; Hollingsworth, L.; Bailey, K. L.; Mehedi, M.

doi:10.1101/2022.10.31.514471

bioRxiv · 10.1101/2022.10.31.514471

RSV-induced Expanded Ciliated Cells Contribute to Bronchial Wall Thickening

Talukdar, S. N.·Osan, J.·Ryan, K.·Grove, B.·Perley, D.·Kumar, B. D.·Yang, S.·Dallman, S.·Hollingsworth, L.·Bailey, K. L.·Mehedi, M.

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Abstract

Viral infection, particularly respiratory syncytial virus (RSV), causes inflammation in the bronchiolar airways (bronchial wall thickening, also known as bronchiolitis), reducing airflow through the bronchioles. This bronchial wall thickening is a common pathophysiological feature in RSV infection, but it causes more fatalities in infants than in children and adults. However, the molecular mechanism of RSV-induced bronchial wall thickening remains unknown, particularly in healthy adults. RSV infection in the airway epithelium of healthy adult bronchial cells reveals RSV-infects primarily ciliated cells. RSV infection expands the cell cytoskeleton substantially without compromising epithelial membrane integrity and ciliary functions. The RSV-induced actin cytoskeleton expansion increases ununiformly epithelial height, and cytoskeletal (actin polymerization), immunological (INF-L1, TNF-, IP10/CXCL10), and viral (NS2) factors are probably responsible. Interestingly, RSV-infected cell cytoskeletons expansion resembles a noncanonical inflammatory phenotype, which contributes to bronchial wall thickening, and is termed cytoskeletal inflammation. Author SummaryRSV infects everyone. Although RSV-induced fatal pathophysiology (e.g., bronchiolitis) is more common in infants than adults, this bronchiolitis (or bronchial wall thickening) is common in the lower respiratory tract due to RSV infection in all ages. To determine the molecular mechanism of RSV-induced bronchial wall thickening, we infected in vitro adult airway epithelium with RSV. We found that RSV-infection induced a substantial actin-cytoskeleton expansion, consequently increased the height of the epithelium. We identified actin polymerization, secretion of proinflammatory cytokines and chemokines, and viral proteins contribute to the RSV-induced cytoskeletal expansion. Our results suggest that RSV-induces a novel noncanonical epithelial host response termed cytoskeletal inflammation, which may contribute to bronchial wall thickening.

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Talukdar, S. N., Osan, J., Ryan, K., Grove, B., Perley, D., Kumar, B. D., Yang, S., Dallman, S., Hollingsworth, L., Bailey, K. L., Mehedi, M.. 2022-11-01. RSV-induced Expanded Ciliated Cells Contribute to Bronchial Wall Thickening. https://doi.org/10.1101/2022.10.31.514471

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