Adenovirus fiber disrupts CAR-mediated intercellular adhesion allowing virus escape.
Adenovirus binds its receptor (CAR), enters cells, and replicates. It must then escape to the environment to infect a new host. We found that following infection, human airway epithelia first released adenovirus to the basolateral surface. Virus then traveled between epithelial cells to emerge on the apical surface. Adenovirus fiber protein, which is produced during viral replication, facilitated apical escape. Fiber binds CAR, which sits on the basolateral membrane where it maintains tight junction integrity. When fiber bound CAR, it disrupted junctional integrity, allowing virus to filter between the cells and emerge apically. Thus, adenovirus exploits its receptor for two important but distinct steps in its life cycle: entry into host cells and escape across epithelial barriers to the environment.
Walters
Robert W
RW
Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, IA 52242, USA.
Freimuth
Paul
P
Moninger
Thomas O
TO
Ganske
Ingrid
I
Zabner
Joseph
J
Welsh
Michael J
MJ
D000256:Adenoviridae / Q000254:growth & development / Q000472:pathogenicity* / Q000648:ultrastructure; D000257:Adenoviridae Infections / Q000503:physiopathology / Q000821:virology; D002213:Capsid / Q000494:pharmacology*; D036022:Capsid Proteins; D002448:Cell Adhesion; D002478:Cells, Cultured; D002923:Cilia / Q000648:ultrastructure; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D017097:Electric Impedance; D006801:Humans; D008954:Models, Biological; D011991:Receptors, Virus / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000166:cytology / Q000648:ultrastructure / Q000821:virology; D019108:Tight Junctions / Q000648:ultrastructure; D013997:Time Factors; D014779:Virus Replication
C568771:CLMP protein, human; D036022:Capsid Proteins; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011991:Receptors, Virus; C018315:hexon capsid protein, Adenovirus