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Journal of Virology, June 2007, p. 5573-5578, Vol. 81, No. 11
0022-538X/07/$08.00+0     doi:10.1128/JVI.02562-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Functional Effects of Coxsackievirus and Adenovirus Receptor Glycosylation on Homophilic Adhesion and Adenoviral Infection{triangledown}

Katherine J. D. Ashbourne Excoffon, Nicholas Gansemer, Geri Traver, and Joseph Zabner*

Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242

Received 20 November 2006/ Accepted 9 March 2007

The coxsackievirus and adenovirus receptor (CAR) is both a viral receptor and homophilic adhesion protein. The extracellular portion of CAR consists of two immunoglobulin (Ig)-like domains, each with a consensus sequence for N-glycosylation. We used chemical, genetic, and biochemical studies to show that both sites are glycosylated and contribute to the function of CAR. Although the glycosylation of CAR does not alter cell surface levels or junctional localization, it affects both adhesion and adenovirus infection in unique ways. CAR-mediated adhesion appears to require at least one site of glycosylation since cells expressing CAR without glycosylation do not cluster with each other. In contrast, glycosylation of the Ig-like domain proximal to the membrane is key to the cooperative behavior of adenovirus binding and infection. Contrary to the hypothesis that cooperativity improves viral infection, our data show that although glycosylation of the D2 domain is required for adenovirus cooperative binding, it has a negative consequence upon infection. This is the first report dissecting the adhesion and receptor activities of CAR, revealing that factors other than the binding interface play a significant role in the function of CAR. These data have important implications for both cancers with altered glycosylation states and cancer treatments using oncolytic adenovirus.


* Corresponding author. Mailing address: University of Iowa, 440 EMRB, Iowa City, IA 52242. Phone: (319) 335-7608. Fax: (319) 335-7623. E-mail: joseph-zabner{at}uiowa.edu

{triangledown} Published ahead of print on 21 March 2007.


Journal of Virology, June 2007, p. 5573-5578, Vol. 81, No. 11
0022-538X/07/$08.00+0     doi:10.1128/JVI.02562-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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