Respiratory syncytial virus infection disrupts monolayer integrity and function in cystic fibrosis airway cells.
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.
Departments of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama 35233, USA. mkong@peds.uab.edu
Michele
M
Kong
Patrick
P
Maeng
Jeong
J
Hong
Rhonda
R
Szczesniak
Eric
E
Sorscher
Wayne
W
Sullender
John Paul
JP
Clancy
D001980:Bronchi / Q000166:cytology / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D006801:Humans; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D012136:Respiratory Syncytial Viruses / Q000502:physiology*
D019005:Cystic Fibrosis Transmembrane Conductance Regulator