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Journal of Virology, November 1998, p. 8669-8675, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Interactions of Soluble Recombinant Integrin
v
5 with Human Adenoviruses
Patricia
Mathias,1
Michael
Galleno,2 and
Glen R.
Nemerow1,*
The Scripps Research Institute, La
Jolla,1 and
Invitrogen,
Carlsbad,2 California
Received 11 June 1998/Accepted 7 August 1998
v integrins have been identified as coreceptors for adenovirus
(Ad) internalization; however, direct interactions of these molecules
with Ad have not been demonstrated. We report here the expression of
soluble integrin
v
5, which retains the ability to recognize the
Ad penton base as well as vitronectin, an Arg Gly Asp (RGD)-containing
extracellular matrix protein. Soluble integrin
v
5 reacted with
seven different Ad serotypes (subgroups A to E) in solid-phase binding
assays. The soluble integrin exhibited different levels of binding to
each Ad serotype; however, binding to multiple Ad types required the
presence of divalent metal cations and was inhibited by a synthetic RGD
peptide, indicating that RGD and cation-binding sequences regulate Ad
interactions with
v
5. Incubation of Ad particles with soluble
v
5 integrin also inhibited subsequent Ad internalization into
epithelial cells as well as virus attachment to monocytic cells. These
findings suggest that soluble
v integrins or antagonists of these
coreceptors could be used to limit infection by multiple Ad types. The
generation of soluble
v integrins should also permit further
detailed kinetic and structural analysis of Ad interactions with its
coreceptors.
*
Corresponding author. Mailing address: Department of
Immunology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (619) 784-8472. Fax: (619) 784-8472. E-mail:
gnemerow{at}scripps.edu.
Journal of Virology, November 1998, p. 8669-8675, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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