Integrin 31 is an alternative cellular receptor for adenovirus serotype 5

Many adenovirus serotypes enter cells by high-affinity binding to the coxsackievirus-adenovirus receptor (CAR) and integrin-mediated internalization. In the present study, we analyzed the possible receptor function of 31 for adenovirus serotype 5 (Ad5). We found that penton base and integrin 31 could interact in vitro. In vivo, both Ad5-cell binding and virus-mediated transduction were inhibited in the presence of anti-3 and anti-1 function-blocking antibodies, and this occurred in both CAR-positive and CAR-negative cell lines. Peptide library screenings and data from binding experiments with wild-type and mutant penton base proteins suggest that the Arg-Gly-Asp (RGD) in the penton base protein, the best known integrin binding motif, is only part of the binding interface with 31, which involved multiple additional contact sites. Adenovirus (Ad) host cell entry requires an initial attach-ment to cells which is mediated by the fiber interaction with the coxsackievirus-Ad receptor (CAR) (2). The subsequent asso-ciation of the capsid protein penton base with integrin mole-cules promotes Ad entry (31). Integrins are a family of struc-turally and functionally related cell surface heterodimeric receptors that mediate cell migration and adhesion. The majo