Loss of epithelial integrity resulting from E-cadherin dysfunction predisposes airway epithelial cells to adenoviral infection.
Epithelial intercellular adhesion is fundamental to the formation of the airway epithelial protective barrier. In this respect, cadherins are important because these adhesion molecules regulate formation and maintenance of epithelial intercellular junctions. To study the importance of airway epithelial integrity in determining susceptibility to virus infection, we used a replication-incompetent adenovirus, RAd35, and an E-cadherin specific function-blocking antibody, SHE78-7, to disrupt intercellular contacts in human bronchial epithelial cell line 16HBE14o- and primary bronchial epithelial cells. After exposure of 16HBE14o- cell cultures to SHE78-7, disruption of the transepithelial permeability barrier was indicated by a loss of transepithelial electrical resistance and an associated increase of mannitol, inulin, and dextran paracellular flux. Subsequent exposure of SHE78-7-treated cell cultures to RAd35 showed a remarkable increase in adenoviral infection as assessed by beta-galactosidase reporter gene expression. In cultures exposed to SHE78-7, disruption of E-cadherin function resulted in infection equivalent to that in control cultures using 16-fold lower viral titers. These studies show that manipulation of E-cadherin function provides a specific means of altering epithelial integrity that in turn determines resistance of airway epithelia to adenoviral infection.
Man
Y
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Cell Biology Department and Clinical Virology Department, Medicines Research Centre, GlaxoWellcome, Stevenage, United Kingdom. ym6862@glaxowellcome.co.uk
Hart
V J
VJ
Ring
C J
CJ
Sanjar
S
S
West
M R
MR
D000257:Adenoviridae Infections / Q000473:pathology* / Q000503:physiopathology*; D000260:Adenoviruses, Human; D015820:Cadherins / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D002460:Cell Line; D004847:Epithelial Cells / Q000473:pathology / Q000502:physiology / Q000821:virology*; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology / Q000821:virology*
D015820:Cadherins