RSV-induced Expanded Ciliated Cells Contribute to Bronchial Wall Thickening

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-α, IP10/CXCL10), and viral (NS2) factors are probably responsible. Interestingly, RSV-infected cell cytoskeleton’s expansion resembles a noncanonical inflammatory phenotype, which contributes to bronchial wall thickening, and is termed cytoskeletal inflammation.

Nuclear translocation of spike mRNA and protein is a novel feature of SARS-CoV-2

“…In this study, we used cells from three donors: nonsmoker healthy adults (donors #1 and #2) and adult with chronic obstructive pulmonary disease 10.3389/fmicb.2023.1073789 Frontiers in Microbiology frontiersin.org (COPD) (donor #3). The protocols for subculturing primary NHBE cells were previously (Osan et al, 2020(Osan et al, , 2021(Osan et al, , 2022Talukdar et al, 2022). Human lung epithelial A549 cells was maintained in F-12 medium (Thermo Fisher Scientific) as described previously (Mehedi et al, 2016).…”

“…The protocols for differentiating primary NHBE cells to form a pseudostratified bronchial airway epithelium were published previously (Osan et al, 2020(Osan et al, , 2021(Osan et al, , 2022Talukdar et al, 2022). Briefly, Transwells (6.5 mm) with 0.4-μm-pore polyester membrane inserts (Corning Inc.) were coated with PureCol (Advanced BioMatrix) for 20 min before cell seeding.…”