Breaking and Entering

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Science  10 Feb 2006:
Vol. 311, Issue 5762, pp. 743
DOI: 10.1126/science.311.5762.743c

In order to establish a productive infection, group B coxsackie viruses (CVBs) (human pathogens that cause meningitis) need to cross an epithelial cell layer during transmission by fecal-oral or respiratory routes. Epithelial cells form a barrier to the passage of molecules and viruses by virtue of tight junctions that effectively seal off one side from the other. Protein components of the tight junction include the coxsackie and adenovirus receptor (CAR), whose virus-binding site is exposed only toward the basolateral surface; viruses approaching from the apical surface (the more likely arrival route) will not be able to access CAR.

Coyne and Bergelson describe how CVBs circumvent this problem of access. Invading virus binds to a protein known as decay-accelerating factor (DAF) on the apical surface of the epithelial cell layer. Binding to DAF triggers the intracellular activation of the Abl kinase, which promotes the rearrangement of the actin cytoskeleton via its effects on the small GTP-binding protein Rac. The actin rearrangements allow the virus to move to the tight junctions, where it can associate with CAR, which leads to virus entry and the eventual delivery of viral RNA into the cytoplasm. At the same time that DAF binding turns on Abl kinase, a kinase called Fyn is activated; this promotes viral recruitment to and internalization via caveolar membranes during the entry process. — SMH

Cell 124, 119 (2006).

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