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Viruses 2013, 5(9), 2260-2271; doi:10.3390/v5092260
Brief Report

Respiratory Syncytial Virus Infection Disrupts Monolayer Integrity and Function in Cystic Fibrosis Airway Cells

1,2,* , 1, 2, 3, 2, 4 and 3
Received: 13 May 2013 / Revised: 12 September 2013 / Accepted: 16 September 2013 / Published: 19 September 2013
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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) Respiratory Syncytial Virus; bronchial epithelial cells; cystic fibrosis; F508del cystic fibrosis transmembrane conductance regulator (CFTR)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

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