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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
14
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pubmed:dateCreated |
2008-4-9
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pubmed:abstractText |
Human species C adenovirus serotype 5 (Ad5) is the most common viral vector used in clinical studies worldwide. Ad5 vectors infect liver cells in vivo with high efficiency via a poorly defined mechanism, which involves virus binding to vitamin K-dependent blood coagulation factors. Here, we report that the major Ad5 capsid protein, hexon, binds human coagulation factor X (FX) with an affinity of 229 pM. This affinity is 40-fold stronger than the reported affinity of Ad5 fiber for the cellular receptor coxsackievirus and adenovirus receptor, CAR. Cryoelectron microscopy and single-particle image reconstruction revealed that the FX attachment site is localized to the central depression at the top of the hexon trimer. Hexon-mutated virus bearing a large insertion in hexon showed markedly reduced FX binding in vitro and failed to deliver a transgene to hepatocytes in vivo. This study describes the mechanism of FX binding to Ad5 and demonstrates the critical role of hexon for virus infection of hepatocytes in vivo.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-10490766,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-10536005,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-10556875,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-11044071,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-11462042,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-11571572,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-12027562,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-12297051,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-12502819,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-12514727,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-12573237,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-12627395,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-12728277,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-12781660,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-12797110,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-12842627,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-12915569,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-14599815,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-14633402,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-14965376,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-15113916,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-15194061,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-15269718,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-15294181,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-15613334,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-15919903,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-15960598,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-16139571,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-16330229,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-16504233,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-16788098,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-16828314,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-17005667,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-17855526,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-8477447,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-9036860,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18391209-9096397
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1091-6490
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
8
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pubmed:volume |
105
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5483-8
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:18391209-Adenovirus Infections, Human,
pubmed-meshheading:18391209-Adenoviruses, Human,
pubmed-meshheading:18391209-Binding Sites,
pubmed-meshheading:18391209-Capsid Proteins,
pubmed-meshheading:18391209-Cells, Cultured,
pubmed-meshheading:18391209-Cryoelectron Microscopy,
pubmed-meshheading:18391209-Factor X,
pubmed-meshheading:18391209-Hepatocytes,
pubmed-meshheading:18391209-Humans,
pubmed-meshheading:18391209-Protein Binding,
pubmed-meshheading:18391209-Virus Attachment
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pubmed:year |
2008
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pubmed:articleTitle |
Adenovirus serotype 5 hexon is critical for virus infection of hepatocytes in vivo.
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pubmed:affiliation |
Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195-7720, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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