Integrin α3β1 Is an Alternative Cellular Receptor for Adenovirus Serotype 5

• Published in: Journal of virology 2003-12, Vol.77 (24), p.13448-13454
• Main Authors: Salone, Barbara, Martina, Yuri, Piersanti, Stefania, Cundari, Enrico, Cherubini, Gioia, Franqueville, Laure, Failla, Cristina M., Boulanger, Pierre, Saggio, Isabella
• Format: Article
• Language: English
• Subjects: Virus-Cell Interactions
• ISSN: 0022-538X; 1098-5514
• DOI: 10.1128/JVI.77.24.13448-13454.2003

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 α3β1 for adenovirus serotype 5 (Ad5). We found that penton base and integrin α3β1 could interact in vitro. In vivo, both Ad5-cell binding and virus-mediated transduction were inhibited in the presence of anti-α3 and anti-β1 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 α3β1, which involved multiple additional contact sites.