Effect of human rhinovirus infection on airway epithelium tight junction protein disassembly and transepithelial permeability. (8th August 2016)

• Record Type: Journal Article
• Authors: Looi, Kevin; Troy, Niamh M.; Garratt, Luke W.; Iosifidis, Thomas; Bosco, Anthony; Buckley, Alysia G.; Ling, Kak-Ming; Martinovich, Kelly M.; Kicic-Starcevich, Elizabeth; Shaw, Nicole C.; Sutanto, Erika N.; Zosky, Graeme R.; Rigby, Paul J.; Larcombe, Alexander N.; Knight, Darryl A.; Kicic, Anthony; Stick, Stephen M.
• Is Part Of: Experimental lung research. Volume 42:Number 7(2016:Aug.)
• Page Start: 380
• Page End: 395
• Publication Date: 2016-08-08
• Subjects: airway epithelial cells -- epithelial barrier -- human rhinovirus -- tight junctions; Lungs -- Periodicals; Lungs -- Diseases -- Periodicals; Lung Diseases; Lung -- physiology; Respiratory System; 616.24
• DOI: 10.1080/01902148.2016.1235237
• Languages: English
• ISSNs: 0190-2148

Abstract

ABSTRACT: Rationale: No studies have assessed the effects of human rhinovirus (HRV) infection on epithelial tight junctions (TJs) and resultant barrier function.Aim of the Study: To correlate viral infection with TJ disassembly, epithelial barrier integrity, and function.Materials and Methods: Human airway epithelial cells were infected with HRV minor serotype 1B (HRV-1B) at various 50% tissue culture infectivity doses (TCID50 ) over 72 hours. HRV replication was assessed by quantitative-polymerase chain reaction (qPCR) while cell viability and apoptosis were assessed by proliferation and apoptotic assays, respectively. Protein expression of claudin-1, occludin, and zonula occludens protein-1 (ZO-1) was assessed using In-Cell™ Western assays. Transepithelial permeability assays were performed to assess effects on barrier functionality. RT 2 Profiler focused qPCR arrays and pathway analysis evaluating associations between human TJ and antiviral response were performed to identify potential interactions and pathways between genes of interests.Results: HRV-1B infection affected viability that was both time and TCID50 dependent. Significant increases in apoptosis and viral replication post-infection correlated with viral titer. Viral infection significantly decreased claudin-1 protein expression at the lower TCID50, while a significant decrease in all three TJ protein expressions occurred at higher TCID50 . Decrease in protein expression was concomitant with significant increases in epithelial permeability of fluorescein isothiocynate labeled-dextran 4 and 20 kDa. Analysis of focused qPCR arrays demonstrated a significant decrease in ZO-1 gene expression. Furthermore, network analysis between human TJ and antiviral response genes revealed possible interactions and regulation of TJ genes via interleukin (IL)-15 in response to HRV-1B infection.Conclusion: HRV-1B infection directly alters human airway epithelial TJ expression leading to increased epithelial permeability potentially via an antiviral response of IL-15.