Virus-induced Abl and Fyn kinase signals permit coxsackievirus entry through epithelial tight junctions

Coyne CB and JM Bergelson. (2006) Cell 124: 119-131.

Group B coxsackieviruses (CVBs) must cross the epithelium as they
initiate infection, but the mechanism by which this occurs remains
uncertain. The coxsackievirus and adenovirus receptor (CAR) is a
component of the tight junction (TJ), and is inaccessible to virus
approaching from the apical surface. Many CVBs also interact with the
GPI-anchored protein decay accelerating factor (DAF). Here we report
that virus attachment to DAF on the apical cell surface activates Abl
kinase, triggering Rac-dependent actin rearrangements that permit virus
movement to the TJ. Within the junction, interaction with CAR promotes
conformational changes in the virus capsid that are essential for virus
entry and release of viral RNA. Interaction with DAF also activates Fyn
kinase, an event that is required for the phosphorylation of caveolin
and transport of virus into the cell within caveolar vesicles. CVBs thus
exploit DAF-mediated signaling pathways to surmount the epithelial
barrier.