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 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.
Coyne
Carolyn B
CB
Division of Infectious Diseases, The Children's Hospital of Philadelphia, University of Pennsylvania, PA 19104, USA.
Bergelson
Jeffrey M
JM
D000199:Actins / Q000502:physiology; D018958:CD55 Antigens / Q000378:metabolism; D018938:Caco-2 Cells; D051242:Caveolin 1 / Q000378:metabolism; D003599:Cytoskeleton / Q000502:physiology / Q000821:virology; D029822:Enterovirus B, Human / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000821:virology; D006801:Humans; D010766:Phosphorylation; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D019108:Tight Junctions / Q000502:physiology* / Q000821:virology; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000378:metabolism
D000199:Actins; D018958:CD55 Antigens; D051242:Caveolin 1; D016315:Proto-Oncogene Proteins c-abl; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases