The cell biology of receptor-mediated virus entry

Grove, Joe; Marsh, Mark

In contrast, adenoviruses exploit both the activities of immune sentinel cells and receptor polarity to penetrate the respiratory epithelium. Adenovirus type 2 uses CAR and 3/5 integrins for productive entry (Wickham et al., 1993; Bergelson et al., 1997; Tomko et al., 1997) . As with CAR, 3 and 5 are located on the basolateral membrane of polarized respiratory epithelial cells, and intact epithelial monolayers are resistant to adenovirus type 2 infection from the apical side. Uptake of adenovirus type 2 into macrophages associated with the apical surface of the epithelium induces the secretion of cytokines, in particular, CXCL8 (IL-8). In response to CXCL8, receptors expressed on respiratory epithelial cells (CXCR1/2) induce redistribution of both 3 and CAR to the apical surface, where they mediate virus entry (Lütschg et al., 2011) . Not only do these examples illustrate the sophisticated ways in which some viruses sequentially exploit distinct cell surface moieties and receptor-signaling activities to successfully mediate infection or overcome the barrier function of epithelia, but they also demonstrate how analyzing virus entry in experimental systems that normal distributions of receptor components and how these distributions are modulated by physiological or viral ligands is likely to provide key insights to how receptor engagement facilitates virus entry and may suggest novel strategies for abrogating these events.