Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-730

Sirena, D; Lilienfeld, B; Eisenhut, M; Kälin, S; Boucke, K; Beerli, R R; Vogt, Lorenz; Ruedl, C; Bachmann, M F; Greber, U F; Hemmi, S (2004). The human membrane cofactor CD46 is a receptor for species B adenovirus serotype 3. Journal of Virology, 78(9):4454-4462.

[img]
Preview
PDF
1MB

View at publisher

Abstract

Many human adenovirus (Ad) serotypes use the coxsackie B virus-Ad receptor (CAR). Recently, CD46 was suggested to be a receptor of species B Ad serotype 11 (Ad11), Ad14, Ad16, Ad21, Ad35, and Ad50. Using Sindbis virus-mediated cDNA library expression, we identify here the membrane cofactor protein CD46 as a surface receptor of species B Ad3. All four major CD46 transcripts and one minor CD46 transcript expressed in nucleated human cells were isolated. Rodent BHK cells stably expressing the BC1 form of CD46 bound radiolabeled Ad3 with a dissociation constant of 0.3 nM, identical to that of CD46-positive HeLa cells expressing twice as many Ad3 binding sites. Pull-down experiments with recombinant Ad3 fibers and a soluble form of the CD46 extracellular domain linked to the Fc portion of human immunoglobulin G (CD46ex-Fc) indicated direct interactions of the Ad3 fiber knob with CD46ex-Fc but not CARex-Fc (Fc-linked extracellular domain of CAR). Ad3 colocalized with cell surface CD46 in both rodent and human cells at the light and electron microscopy levels. Anti-CD46 antibodies and CD46ex-Fc inhibited Ad3 binding to CD46-expressing BHK cells more than 10-fold and to human cells 2-fold. In CD46-expressing BHK cells, wild-type Ad3 and a chimeric Ad consisting of the Ad5 capsid and the Ad3 fiber elicited dose-dependent cytopathic effects and transgene expression, albeit less efficiently than in human cells. Together, our results show that all of the major splice forms of CD46 are predominant and functional binding sites of Ad3 on CD46-expressing rodent and human cells but may not be the sole receptor of species B Ads on human cells. These results have implications for understanding viral pathogenesis and therapeutic gene delivery.

Citations

166 citations in Web of Science®
165 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

158 downloads since deposited on 11 Feb 2008
22 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
DDC:570 Life sciences; biology
Language:English
Date:1 May 2004
Deposited On:11 Feb 2008 12:17
Last Modified:27 Nov 2013 21:54
Publisher:American Society for Microbiology
ISSN:0022-538X
Publisher DOI:10.1128/JVI.78.9.4454-4462.2004
PubMed ID:15078926

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page