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Journal of Virology, October 1998, p. 7909-7915, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

The Coxsackievirus-Adenovirus Receptor Protein Can Function as a Cellular Attachment Protein for Adenovirus Serotypes from Subgroups A, C, D, E, and F

Peter W. Roelvink,1,* Alena Lizonova,1 Jennifer G. M. Lee,1 Yuan Li,1 Jeffrey M. Bergelson,2 Robert W. Finberg,3 Douglas E. Brough,1 Imre Kovesdi,1 and Thomas J. Wickham1

GenVec Inc., Rockville, Maryland 208521; Division of Immunologic and Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 191042; and Division of Infectious Diseases, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 021153

Received 17 March 1998/Accepted 17 June 1998

Attachment of an adenovirus (Ad) to a cell is mediated by the capsid fiber protein. To date, only the cellular fiber receptor for subgroup C serotypes 2 and 5, the so-called coxsackievirus-adenovirus receptor (CAR) protein, has been identified and cloned. Previous data suggested that the fiber of the subgroup D serotype Ad9 also recognizes CAR, since Ad9 and Ad2 fiber knobs cross-blocked each other's cellular binding. Recombinant fiber knobs and 3H-labeled Ad virions from serotypes representing all six subgroups (A to F) were used to determine whether the knobs cross-blocked the binding of virions from different subgroups. With the exception of subgroup B, all subgroup representatives cross-competed, suggesting that they use CAR as a cellular fiber receptor as well. This result was confirmed by showing that CAR, produced in a soluble recombinant form (sCAR), bound to nitrocellulose-immobilized virions from the different subgroups except subgroup B. Similar results were found for blotted fiber knob proteins. The subgroup F virus Ad41 has both short and long fibers, but only the long fiber bound sCAR. The sCAR protein blocked the attachment of all virus serotypes that bound CAR. Moreover, CHO cells expressing human CAR, in contrast to untransformed CHO cells, all specifically bound the sCAR-binding serotypes. We conclude therefore that Ad serotypes from subgroups A, C, D, E, and F all use CAR as a cellular fiber receptor.

* Corresponding author. Mailing address: GenVec Inc., 12111 Parklawn Dr., Rockville, MD 20852. Phone: (301) 816-5548. Fax: (301) 816-0440. E-mail: roelvink{at}genvec.com.

Journal of Virology, October 1998, p. 7909-7915, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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