Basolateral localization of fiber receptors limits adenovirus infection from the apical surface of airway epithelia

Recent identification of two receptors for the adenovirus fiber protein, co xsackie B and adenovirus type 2 and 5 receptor (CAR), and the major histoco mpatibility complex (MHC) Class I alpha-2 domain allows the molecular basis of adenoviral infection to be investigated. Earlier work has shown that hu man airway epithelia are resistant to infection by adenovirus, Therefore, w e examined the expression and localization of CAR and MHC Class I in an in vitro model of well differentiated, ciliated human airway epithelia. We fou nd that airway epithelia express CAR and MHC Class I. However, neither rece ptor was present in the apical membrane; instead, both were polarized to th e basolateral membrane. These findings explain the relative resistance to a denovirus infection from the apical surface. In contrast, when the virus wa s applied to the basolateral surface, gene transfer was much more efficient because of an interaction of adenovirus fiber with its receptors, In addit ion, when the integrity of the tight junctions was transiently disrupted, a pically applied adenovirus gained access to the basolateral surface and enh anced gene transfer. These data suggest that the receptors required for eff icient infection are not available on the apical surface, and interventions that allow access to the basolateral space where fiber receptors are locat ed increase gene transfer efficiency.