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TitleAdenovirus serotype 5 hexon mediates liver gene transfer.
Journal, issue, pagesCell, Vol. 132, Issue 3, Page 397-409, Year 2008
Publish dateFeb 8, 2008
AuthorsSimon N Waddington / John H McVey / David Bhella / Alan L Parker / Kristeen Barker / Hideko Atoda / Rebecca Pink / Suzanne M K Buckley / Jenny A Greig / Laura Denby / Jerome Custers / Takashi Morita / Ivo M B Francischetti / Robson Q Monteiro / Dan H Barouch / Nico van Rooijen / Claudio Napoli / Menzo J E Havenga / Stuart A Nicklin / Andrew H Baker /
PubMed AbstractAdenoviruses 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, ...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.
External linksCell / PubMed:18267072
MethodsEM (single particle)
Resolution23.0 Å
Structure data

EMDB-1464:
Adenovirus serotype 5 hexon mediates liver gene transfer.
Method: EM (single particle) / Resolution: 23.0 Å

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