Evidence map›Paper›PMID 12610146›Full record

ArticleJournal of virology2003

The interaction between the fiber knob domain and the cellular attachment receptor determines the intracellular trafficking route of adenoviruses.

Dmitry M Shayakhmetov, Zong-Yi Li, Vladimir Ternovoi, Anuj Gaggar, Helen Gharwan, André Lieber

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
7.0field-weighted citation impact, top 3% 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

64 citing papers in PubMed, 120 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Targeting Antigen to the Surface of EVs Improves theMolecular therapy. Methods & clinical development · 2020
    Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

4 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

6 authors at 1 institution in 2 countries.

Dmitry M ShayakhmetovDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington 98195, USA.
Zong-Yi Li
Vladimir Ternovoi
Anuj Gaggar
Helen Gharwan
André Lieber
Medical Genetics Center · DE

Funding

VECTOR CONSTRUCTIONS FOR GENE THERAPY OF SICKLE CELL DISEASEP01HL053750 · NHLBI · UNIVERSITY OF WASHINGTON · PI RUSSELL, DAVID W · 1994 to 2014
$30.4M
NHLBI NIH HHS HL-00-008NHLBI NIH HHS P01 HL053750NHLBI NIH HHS P0I HL 53750
6 · The paper itself

Abstract

Most of the presently used adenovirus (Ad) vectors are based on serotype 5. However, the application of these vectors is limited by the native tropism of Ad5. To address this problem, a series of fiber chimeric vectors were produced to take advantage of the different cellular receptors used by Ad of different subgroups. In this study we utilize an Ad5-based chimeric vector containing sequences encoding the Ad35 fiber knob domain instead of the Ad5 knob (Ad5/35L) to analyze factors responsible for selection of intracellular trafficking routes by Ads. By competition analysis with recombinant Ad5 and Ad35 knobs we showed that the Ad5/35L vector infected cells through a receptor different from the Ad5 receptor. Intracellular trafficking of Ad5 and Ad5/35L viruses was analyzed in HeLa cells by tracking fluorophore-conjugated Ad particles, by immunostaining for capsid hexon protein, by electron microscopy, and by Southern blotting for viral DNA. These studies showed that the interaction with the Ad35 receptor(s) predestines Ad5/35L vector to intracellular trafficking pathways different from those of Ad5. Ad5 efficiently escaped from the endosomes early after infection. In contrast, Ad5/35L remained longer in late endosomal/lysosomal compartments and used them to achieve localization to the nucleus. However, a significant portion of Ad5/35L particles appeared to be recycled back to the cell surface. This phenomenon resulted in significantly less efficient Ad5/35L-mediated gene transfer compared to that of Ad5. We also demonstrated that the selection of intracellular trafficking routes was determined by the fiber knob domain and did not depend on the length of the fiber shaft. This study contributes to a better understanding of the mechanisms that govern the infection of retargeted, capsid-modified vectors which have potential application for hematopoietic stem cell and tumor gene therapy.

Indexed as

Adenoviruses, HumanBiological TransportCapsid ProteinsCell LineCell NucleusEndosomesGenetic VectorsGreen Fluorescent ProteinsHeLa CellsHumansLuminescent ProteinsLysosomesMicroscopy, ElectronReceptors, VirusRecombinant Fusion ProteinsCapsid ProteinsGreen Fluorescent Proteinshexon capsid protein, AdenovirusLuminescent ProteinsReceptors, VirusRecombinant Fusion Proteins

Identifiers

PMID12610146
PMCPMC149506
OpenAlexW1980663819

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.