Adenovirus serotype 5 hexon mediates liver gene transfer

Waddington, S. et al. (2008) Adenovirus serotype 5 hexon mediates liver gene transfer. Cell, 132(3), pp. 397-409. (doi: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:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bhella, Dr David and Nicklin, Professor Stuart and Baker, Professor Andrew and Denby, Dr Laura and Parker, Dr Alan
Authors: Waddington, S., McVey, J.H., Bhella, D., Parker, A., Barker, K., Atoda, H., Pink, R., Buckley, S.M.K., Greig, J., Denby, L., Custers, J., Morita, T., Francischetti, I.M.B., Monteiro, R.Q., Barouch, D.H., van Rooijen, R.N., Napoli, C., Havenga, M.J.E., Nicklin, S.A., and Baker, A.H.
Subjects:R Medicine > RC Internal medicine
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Cell
ISSN:0092-8674
ISSN (Online):1097-4172
Published Online:07 February 2008

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