Integrin alpha3beta1 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 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.
Salone
Barbara
B
Department of Genetics and Molecular Biology, University of Rome "La Sapienza," Rome, Italy.
Martina
Yuri
Y
Piersanti
Stefania
S
Cundari
Enrico
E
Cherubini
Gioia
G
Franqueville
Laure
L
Failla
Cristina M
CM
Boulanger
Pierre
P
Saggio
Isabella
I
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
D036022:Capsid Proteins; D039201:Integrin alpha3beta1; D019151:Peptide Library; D011991:Receptors, Virus; C043322:penton protein, adenovirus