The cell adhesion molecule "CAR" and sialic acid on human erythrocytes influence adenovirus in vivo biodistribution.

Details

Serval ID
serval:BIB_306A2BD5E28E
Type
Article: article from journal or magazin.
Collection
Publications
Title
The cell adhesion molecule "CAR" and sialic acid on human erythrocytes influence adenovirus in vivo biodistribution.
Journal
Plos Pathogens
Author(s)
Seiradake E., Henaff D., Wodrich H., Billet O., Perreau M., Hippert C., Mennechet F., Schoehn G., Lortat-Jacob H., Dreja H., Ibanes S., Kalatzis V., Wang J.P., Finberg R.W., Cusack S., Kremer E.J.
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
5
Number
1
Pages
e1000277
Language
english
Notes
Publication types: Journal Article
Abstract
Although it has been known for 50 years that adenoviruses (Ads) interact with erythrocytes ex vivo, the molecular and structural basis for this interaction, which has been serendipitously exploited for diagnostic tests, is unknown. In this study, we characterized the interaction between erythrocytes and unrelated Ad serotypes, human 5 (HAd5) and 37 (HAd37), and canine 2 (CAV-2). While these serotypes agglutinate human erythrocytes, they use different receptors, have different tropisms and/or infect different species. Using molecular, biochemical, structural and transgenic animal-based analyses, we found that the primary erythrocyte interaction domain for HAd37 is its sialic acid binding site, while CAV-2 binding depends on at least three factors: electrostatic interactions, sialic acid binding and, unexpectedly, binding to the coxsackievirus and adenovirus receptor (CAR) on human erythrocytes. We show that the presence of CAR on erythrocytes leads to prolonged in vivo blood half-life and significantly reduced liver infection when a CAR-tropic Ad is injected intravenously. This study provides i) a molecular and structural rationale for Ad-erythrocyte interactions, ii) a basis to improve vector-mediated gene transfer and iii) a mechanism that may explain the biodistribution and pathogenic inconsistencies found between human and animal models.
Keywords
Adenoviridae/pathogenicity, Animals, Binding Sites, Cell Adhesion Molecules/metabolism, Dogs, Erythrocytes/pathology, Erythrocytes/virology, Hemagglutination, Humans, N-Acetylneuraminic Acid/metabolism
Pubmed
Open Access
Yes
Create date
24/10/2014 13:58
Last modification date
20/08/2019 14:15
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