title: Integrin alpha3beta1 is an alternative cellular receptor for adenovirus serotype 5.
abstract: 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 alpha3beta1 for adenovirus serotype 5 (Ad5). We found that penton base and integrin alpha3beta1 could interact in vitro. In vivo, both Ad5-cell binding and virus-mediated transduction were inhibited in the presence of anti-alpha3 and anti-beta1 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 alpha3beta1, which involved multiple additional contact sites.
authors.affiliation: Department of Genetics and Molecular Biology, University of Rome "La Sapienza," Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Salone
authors.forename: Yuri
authors.initials: Y
authors.lastname: Martina
authors.forename: Stefania
authors.initials: S
authors.lastname: Piersanti
authors.forename: Enrico
authors.initials: E
authors.lastname: Cundari
authors.forename: Gioia
authors.initials: G
authors.lastname: Cherubini
authors.forename: Laure
authors.initials: L
authors.lastname: Franqueville
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Failla
authors.forename: Pierre
authors.initials: P
authors.lastname: Boulanger
authors.forename: Isabella
authors.initials: I
authors.lastname: Saggio
mesh_terms: D000260:Adenoviruses, Human / Q000378:metabolism / Q000472:pathogenicity*; D000595:Amino Acid Sequence; D036022:Capsid Proteins / Q000378:metabolism; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D039201:Integrin alpha3beta1 / Q000378:metabolism*; D008969:Molecular Sequence Data; D019151:Peptide Library; D011991:Receptors, Virus / Q000378:metabolism*; D012703:Serotyping
chemical_list: D036022:Capsid Proteins; D039201:Integrin alpha3beta1; D019151:Peptide Library; D011991:Receptors, Virus; C043322:penton protein, adenovirus