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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Adenovirus Serotype 5 Hexon Mediates Liver Gene Transfer
Cell, Volume 132, No. 3, Year 2008
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Description
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. © 2008 Elsevier Inc. All rights reserved.
Authors & Co-Authors
Waddington, Simon N.
United Kingdom, London
Ucl Cancer Institute
McVey, John H.
United Kingdom, London
Imperial College London
Parker, Alan L.
United Kingdom, Glasgow
University of Glasgow
Buckley, Suzanne M.K.
United Kingdom, London
Ucl Cancer Institute
Francischetti, Ivo M.B.
United States, Bethesda
National Institutes of Health Nih
Monteiro, Robson Q.
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Barouch, Dan H.
United States, Boston
Beth Israel Deaconess Medical Center
Van-Rooijen, Nico
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Napoli, Claudio
Italy, Naples
Università Degli Studi Di Napoli Federico Ii
United States, Philadelphia
Temple University
Havenga, Menzo J.E.
Netherlands, Leiden
Crucell nv
Nicklin, Stuart A.
United Kingdom, Glasgow
University of Glasgow
Baker, Andrew H.
United Kingdom, Glasgow
University of Glasgow
Statistics
Citations: 528
Authors: 12
Affiliations: 12
Identifiers
Doi:
10.1016/j.cell.2008.01.016
ISSN:
00928674
Research Areas
Genetics And Genomics