The polarized cells that line our digestive and respiratory tracts form a tight barrier that protects our bodies from viruses. Understanding how viruses are able to breach these polarized epithelial cells is important in guiding the development of therapeutics and vaccines, yet previous research has focused mainly on in vitro studies of virus entry into nonpolarized cells. Microscopy advances have recently allowed the high-resolution imaging of virus entry in polarized epithelial cells. Boulant and colleagues used live-cell spinning-disk confocal microscopy to follow the uptake of single mammalian reovirus (MRV) virions and infectious subvirion particles (ISVPs) in polarized Madin–Darby canine kidney cells. Both virus particles were internalized by clathrin-mediated endocytosis at the apical surface. MRV virions reached early and late endosomes, while ISVPs escaped the endocytic pathway prior to reaching early endosomes. In the images above, the tight-junction protein ZO-1 (red, left) shows the typical belt pattern surrounding the polarized cells (side views are also shown in the top and side strips). The MRV cell surface receptor JAM-A (red, right) is localized near tight junctions and on the apical side of the cells.

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