Virus-Induced Abl and Fyn Kinase Signals Permit Coxsackievirus Entry through Epithelial Tight Junctions

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 and is inaccessible to virus approaching from the apical surface. Many...

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Veröffentlicht in:Cell 2006-01, Vol.124 (1), p.119-131
Hauptverfasser: Coyne, Carolyn B., Bergelson, Jeffrey M.
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description 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 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 tight junction. 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.
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subjects Actins - physiology
Adenovirus
Caco-2 Cells
Caveolin 1 - metabolism
CD55 Antigens - metabolism
Coxsackievirus
Cytoskeleton - physiology
Cytoskeleton - virology
Enterovirus B, Human - metabolism
Epithelial Cells - metabolism
Epithelial Cells - virology
Humans
Phosphorylation
Proto-Oncogene Proteins c-abl - metabolism
Proto-Oncogene Proteins c-fyn - metabolism
Signal Transduction - physiology
src-Family Kinases - metabolism
Tight Junctions - physiology
Tight Junctions - virology
Tumor Cells, Cultured
title Virus-Induced Abl and Fyn Kinase Signals Permit Coxsackievirus Entry through Epithelial Tight Junctions
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