Adenovirus type 5 pseudotyped with adenovirus type 37 fiber uses sialic acid as a cellular receptor.

Abstract:

:For purposes of gene therapy, the tropism of adenovirus (Ad) serotype 5 vectors can be altered with fibers derived from alternative serotypes. However, there is currently limited information available on the cellular receptors used by the approximately 51 known Ad serotypes. Recently, alpha(2-->3)-linked sialic acid (2,3-SA) has been implicated as the cellular receptor for wild-type Ad37. However, some studies have demonstrated that wild-type Ad37 uses a 50-kDa protein and not sialic acid as its primary receptor for binding of human conjunctival cells. The sialic acid receptor has also been shown not to play a major role in the infection of these cells by an Ad5 virion pseudotyped with Ad37 fiber (Ad5.GFP.DeltaF/37F). In this study, we demonstrate that a similar virus (Ad5F37) can indeed use alpha(2-->3)-linked sialic acid as a cellular receptor. We also find that the receptor used by Ad5F37 is sensitive to proteases and that Ad5F37 can use integrin more efficiently than sialic acid for cell entry. Unlike Ad5 vectors, Ad5F37 does not efficiently employ the coxsackie and adenovirus receptor (CAR) to infect cells. Similar to Ad5, Ad5F37 infection of cells that form tight junctions can be enhanced by ethylenediaminetetraacetic acid (EDTA). These results have implications in the design of pseudotyped adenovirus vectors for gene therapy and may have particular use in the treatment of diseases involving breakdown of the blood-retinal barrier.

journal_name

Virology

journal_title

Virology

authors

Cashman SM,Morris DJ,Kumar-Singh R

doi

10.1016/j.virol.2004.04.001

subject

Has Abstract

pub_date

2004-06-20 00:00:00

pages

129-39

issue

1

eissn

0042-6822

issn

1096-0341

pii

S004268220400217X

journal_volume

324

pub_type

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