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

Viruses

Kong Michele⁴  Maeng Patrick⁴  Hong Jeong³  Szczesniak Rhonda¹  Sorscher Eric³  Sullender Wayne² 

[1] Departments of Pulmonary Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229, USA;Center for Global Health, Colorado School of Public Health, 13199 E Montview Blvd, Suite 310, A090 Aurora, CO 80045, USA;The Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, 35233, USA;Departments of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama 35233, USA

关键词: Respiratory Syncytial Virus;    bronchial epithelial cells;    cystic fibrosis;    F508del cystic fibrosis transmembrane conductance regulator (CFTR);   

DOI  :  10.3390/v5092260

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.