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Adenovirus serotype 5 hexon mediates liver gene transfer

Waddington, Simon N., Mcvey, John H., Bhella, David, Parker, Alan L., Barker, Kristeen, Atoda, Hideko, Pink, Rebecca, Buckley, Suzanne M. K., Greig, Jenny A., Denby, Laura, Custers, Jerome, Morita, Takashi, Francischetti, Ivo M. B., Monteiro, Robson Q., Barouch, Dan H., van Rooijen, Nico, Napoli, Claudio, Havenga, Menzo J. L., Nicklin, Stuart A. and Baker, Andrew H. 2008. Adenovirus serotype 5 hexon mediates liver gene transfer. Cell 132 (3) , pp. 397-409. 10.1016/j.cell.2008.01.016

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Abstract

Adenoviruses are used extensively as gene transfer agents, both experimentally and clinically. However, targeting of liver cells by adenoviruses compromises their potential efficacy. In cell culture, the adenovirus serotype 5 fiber protein engages the coxsackievirus and adenovirus receptor (CAR) to bind cells. Paradoxically, following intravascular delivery, CAR is not used for liver transduction, implicating alternate pathways. Recently, we demonstrated that coagulation factor (F)X directly binds adenovirus leading to liver infection. Here, we show that FX binds to the Ad5 hexon, not fiber, via an interaction between the FX Gla domain and hypervariable regions of the hexon surface. Binding occurs in multiple human adenovirus serotypes. Liver infection by the FX-Ad5 complex is mediated through a heparin-binding exosite in the FX serine protease domain. This study reveals an unanticipated function for hexon in mediating liver gene transfer in vivo.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > RB Pathology
Uncontrolled Keywords: microbio; humdisease
Publisher: Cell Press
ISSN: 0092-8674
Last Modified: 04 Jun 2017 04:42
URI: http://orca.cf.ac.uk/id/eprint/43256

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