Send to:

Choose Destination
See comment in PubMed Commons below
Am J Respir Crit Care Med. 2008 Dec 15;178(12):1271-81. doi: 10.1164/rccm.200801-136OC. Epub 2008 Sep 11.

Rhinovirus disrupts the barrier function of polarized airway epithelial cells.

Author information

  • 1Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI 48109-0688, USA.



Secondary bacterial infection following rhinovirus (RV) infection has been recognized in chronic obstructive pulmonary disease.


We sought to understand mechanisms by which RV infection facilitates secondary bacterial infection.


Primary human airway epithelial cells grown at air-liquid interface and human bronchial epithelial (16HBE14o-) cells grown as polarized monolayers were infected apically with RV. Transmigration of bacteria (nontypeable Haemophilus influenzae and others) was assessed by colony counting and transmission electron microscopy. Transepithelial resistance (R(T)) was measured by using a voltmeter. The distribution of zona occludins (ZO)-1 was determined by immunohistochemistry and immunoblotting.


Epithelial cells infected with RV showed 2-log more bound bacteria than sham-infected cultures, and bacteria were recovered from the basolateral media of RV- but not sham-infected cells. Infection of polarized airway epithelial cell cultures with RV for 24 hours caused a significant decrease in R(T) without causing cell death or apoptosis. Ultraviolet-treated RV did not decrease R(T), suggesting a requirement for viral replication. Reduced R(T) was associated with increased paracellular permeability, as determined by flux of fluorescein isothiocyanate (FITC)-inulin. Neutralizing antibodies to tumor necrosis factor (TNF)-alpha, IFN-gamma and IL-1beta reversed corresponding cytokine-induced reductions in R(T) but not that induced by RV, indicating that the RV effect is independent of these proinflammatory cytokines. Confocal microscopy and immunoblotting revealed the loss of ZO-1 from tight junction complexes in RV-infected cells. Intranasal inoculation of mice with RV1B also caused the loss of ZO-1 from the bronchial epithelium tight junctions in vivo.


RV facilitates binding, translocation, and persistence of bacteria by disrupting airway epithelial barrier function.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Atypon Icon for PubMed Central
    Loading ...
    Write to the Help Desk