Evidence map›Paper›PMID 18391209›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2008

Adenovirus serotype 5 hexon is critical for virus infection of hepatocytes in vivo.

O Kalyuzhniy, N C Di Paolo, M Silvestry, S E Hofherr, M A Barry, P L Stewart, D M Shayakhmetov

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 214 papers.

0numbers the graph read from it
0cells of the map it votes in
214citing papers in PubMed
25.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

214 citing papers in PubMed, 348 citations in OpenAlex.

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  9. Molecular therapy. Methods & clinical development · 2025
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  15. Article
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  17. Viral platform engineering for targeted gene delivery to human hematopoietic stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  18. Article
  19. Article
  20. FAP-retargeted Ad5 enables in vivo gene delivery to stromal cells in the tumor microenvironment.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article

154 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

O KalyuzhniyDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195-7720, USA.
N C Di Paolo
M Silvestry
S E Hofherr
M A Barry
P L Stewart
D M Shayakhmetov
University of Washington Medical Center · USVanderbilt University Medical Center · USBaylor College of Medicine · USMayo Clinic in Arizona · US

Funding

MOLECULAR BIOPHYSICS TRAINING PROGRAM AT VANDERBILTT32GM008320 · NIGMS · VANDERBILT UNIVERSITY · PI CHAZIN, WALTER J. · 1989 to 2023
$7.9M
Innate immunity to adenovirus vectorsR01AI065429 · NIAID · UNIVERSITY OF WASHINGTON · PI SHAYAKHMETOV, DMITRY · 2005 to 2019
$5.6M
Cryo-EM Structural Studies of Adenovirus Cell EntryR01AI042929 · NIAID · VANDERBILT UNIVERSITY · PI STEWART, PHOEBE L · 2004 to 2010
$2.8M
Hexon-modified adenovirus vectorsR21AI064882 · NIAID · UNIVERSITY OF WASHINGTON · PI SHAYAKHMETOV, DMITRY · 2006 to 2007
$422k
Targeted adenovirus vectors for systemic applicationR21AI062853 · NIAID · UNIVERSITY OF WASHINGTON · PI SHAYAKHMETOV, DMITRY · 2005 to 2006
$400k
CRYO-EM STRUCTURAL STUDIES OF ADENOVIRUS CELL ENTRYR29AI042929 · NIAID · VANDERBILT UNIVERSITY · PI STEWART, PHOEBE L · 1997 to 2001
$214k
NIAID NIH HHS AI042929NIAID NIH HHS AI062853NIAID NIH HHS AI064882NIAID NIH HHS AI065429NIAID NIH HHS R01 AI042929NIAID NIH HHS R01 AI065429NIAID NIH HHS R21 AI062853NIAID NIH HHS R21 AI064882NIAID NIH HHS R29 AI042929NIGMS NIH HHS T32 GM008320
6 · The paper itself

Abstract

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.

Indexed as

Virus AttachmentAdenoviruses, HumanAdenovirus Infections, HumanBinding SitesCapsid ProteinsCells, CulturedCryoelectron MicroscopyFactor XHepatocytesHumansProtein BindingCapsid ProteinsFactor Xhexon capsid protein, Adenovirus

Identifiers

PMID18391209
PMCPMC2291105
OpenAlexW2079523736

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.