Abstract: Background: Respiratory Syncytial Virus (RSV) infection is a common contributor to pulmonary symptoms in children with cystic fibrosis (CF). Here we examined RSV infection in immortalized bronchial epithelial cells (CFBE41o-) expressing wild-type (wt) or F508del cystic fibrosis transmembrane conductance regulator (CFTR), for monolayer integrity and RSV replication. Methods: CFBE41o- monolayers expressing wt or F508del CFTR were grown on permeable supports and inoculated with RSV A2 strain. Control experiments utilized UV-inactivated RSV and heat-killed RSV. Monolayer resistance and RSV production was monitored for up to six days post-infection. Results: Within 24 h, a progressive decrease in monolayer resistance was observed in RSV infected F508del CFBE41o- cells, while the monolayer integrity of RSV infected wt CFTR CFBE41o- cells remained stable. RSV replication was necessary to disrupt F508del CFBE41o- monolayers as UV-irradiated and heat killed RSV had no effect on monolayer integrity, with an earlier and much more pronounced peak in RSV titer noted in F508del relative to wt CFTR-expressing cells. RSV infection of wt CFBE41o- monolayers also resulted in blunting of CFTR response. Conclusions: These findings identify an enhanced sensitivity of CFBE41o- cells expressing F508del CFTR to RSV infection, replication and monolayer disruption independent of the cellular immune response, and provide a novel mechanism by which cystic fibrosis airway epithelia are susceptible to RSV-dependent injury.
Keywords: Respiratory Syncytial Virus; bronchial epithelial cells; cystic fibrosis; F508del cystic fibrosis transmembrane conductance regulator (CFTR)
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Kong, M.; Maeng, P.; Hong, J.; Szczesniak, R.; Sorscher, E.; Sullender, W.; Clancy, J.P. Respiratory Syncytial Virus Infection Disrupts Monolayer Integrity and Function in Cystic Fibrosis Airway Cells. Viruses 2013, 5, 2260-2271.
Kong M, Maeng P, Hong J, Szczesniak R, Sorscher E, Sullender W, Clancy JP. Respiratory Syncytial Virus Infection Disrupts Monolayer Integrity and Function in Cystic Fibrosis Airway Cells. Viruses. 2013; 5(9):2260-2271.
Kong, Michele; Maeng, Patrick; Hong, Jeong; Szczesniak, Rhonda; Sorscher, Eric; Sullender, Wayne; Clancy, John P. 2013. "Respiratory Syncytial Virus Infection Disrupts Monolayer Integrity and Function in Cystic Fibrosis Airway Cells." Viruses 5, no. 9: 2260-2271.