Functional effects of coxsackievirus and adenovirus receptor glycosylation on homophilic adhesion and adenoviral infection

Katherine J D Ashbourne Excoffon; Nicholas Gansemer; Geri Traver; Joseph Zabner

doi:10.1128/JVI.02562-06

Back

Functional effects of coxsackievirus and adenovirus receptor glycosylation on homophilic adhesion and adenoviral infection

Journal article

Open access

Peer reviewed

Functional effects of coxsackievirus and adenovirus receptor glycosylation on homophilic adhesion and adenoviral infection

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

Journal of virology, Vol.81(11), pp.5573-5578

06/2007

DOI: 10.1128/JVI.02562-06

PMCID: PMC1900266

PMID: 17376928

Files and links (1)

url

https://doi.org/10.1128/JVI.02562-06View

Published (Version of record) Open Access

Abstract

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.

Adenoviridae Infections - pathology

Adenoviridae Infections - virology

Cell Adhesion - genetics

Mutagenesis, Site-Directed

Enterovirus - physiology

Cercopithecus aethiops

Adenoviridae - physiology

Glycosylation

Coxsackie and Adenovirus Receptor-Like Membrane Protein

Receptors, Virus - genetics

Receptors, Virus - physiology

Animals

Enterovirus - genetics

Receptors, Virus - chemistry

Cell Adhesion - physiology

Adenoviridae - genetics

COS Cells

Details

Title: Subtitle: Functional effects of coxsackievirus and adenovirus receptor glycosylation on homophilic adhesion and adenoviral infection
Creators: Katherine J D Ashbourne Excoffon - Department of Internal Medicine, University of Iowa, 440 EMRB, Iowa City, IA 52242, USA
Nicholas Gansemer
Geri Traver
Joseph Zabner
Resource Type: Journal article
Publication Details: Journal of virology, Vol.81(11), pp.5573-5578
DOI: 10.1128/JVI.02562-06
PMID: 17376928
PMCID: PMC1900266
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Grant note: P01 HL051670 / NHLBI NIH HHS HL51670-11 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS DK54759 / NIDDK NIH HHS
Language: English
Date published: 06/2007
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
Record Identifier: 9984094546902771

Metrics

36 Record Views

34 Times Cited - Web of Science