Evidence map›Paper›PMID 11462042›Full record

ArticleJournal of virology2001

Apical localization of the coxsackie-adenovirus receptor by glycosyl-phosphatidylinositol modification is sufficient for adenovirus-mediated gene transfer through the apical surface of human airway epithelia.

R W Walters, W van't Hof, S M Yi, M K Schroth, J Zabner, R G Crystal, M J Welsh

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

23 citing papers in PubMed, 51 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Adenovirus serotype 5 hexon is critical for virus infection of hepatocytes in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2008
    Article
  11. Article
  12. Article
  13. Article
  14. The role of the extracellular domain in the biology of the coxsackievirus and adenovirus receptor.American journal of respiratory cell and molecular biology · 2005
    Article
  15. Article
  16. Digitoxin mimics gene therapy with CFTR and suppresses hypersecretion of IL-8 from cystic fibrosis lung epithelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2004
    Article
  17. Article
  18. Article
  19. Article
  20. Article
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 5 institutions in 2 countries.

R W WaltersHoward Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
W van't Hof
S M Yi
M K Schroth
J Zabner
R G Crystal
M J Welsh
Institute of Molecular Biology and Biophysics · RUCornell University · USHoward Hughes Medical Institute · USPulmonary and Critical Care Associates · USUniversity of Wisconsin–Madison · US

Funding

Vector CoreP01HL051670 · NHLBI · UNIVERSITY OF IOWA · PI MCCRAY, PAUL B · 1993 to 2019
$36.5M
UNIDIRECTIONAL TRAFFICKING OF ADENOVIRUS VECTORSP01HL051746 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI WIVEL, NELSON A. · 1993 to 2008
$19.3M
NHLBI NIH HHS HL51670NHLBI NIH HHS P01 HL051670NHLBI NIH HHS P01 HL051746NHLBI NIH HHS P01 HL51746-08
6 · The paper itself

Abstract

In well-differentiated human airway epithelia, the coxsackie B and adenovirus type 2 and 5 receptor (CAR) resides primarily on the basolateral membrane. This location may explain the observation that gene transfer is inefficient when adenovirus vectors are applied to the apical surface. To further test this hypothesis and to investigate requirements and barriers to apical gene transfer to differentiated human airway epithelia, we expressed CAR in which the transmembrane and cytoplasmic tail were replaced by a glycosyl-phosphatidylinositol (GPI) anchor (GPI-CAR). As controls, we expressed wild-type CAR and CAR lacking the cytoplasmic domain (Tailless-CAR). All three constructs enhanced gene transfer with similar efficiencies in fibroblasts. In airway epithelia, GPI-CAR localized specifically to the apical membrane, where it bound adenovirus and enhanced gene transfer to levels obtained when vector was applied to the basolateral membrane. Moreover, GPI-CAR facilitated gene transfer of the cystic fibrosis transmembrane conductance regulator to cystic fibrosis airway epithelia, correcting the Cl(-) transport defect. In contrast, when we expressed wild-type CAR it localized to the basolateral membrane and failed to increase apical gene transfer. Only a small amount of Tailless-CAR resided in the apical membrane, and the effects on apical virus binding and gene transfer were minimal. These data indicate that binding of adenovirus to an apical membrane receptor is sufficient to mediate effective gene transfer to human airway epithelia and that the cytoplasmic domain of CAR is not required for this process. The results suggest that targeting apical receptors in differentiated airway epithelia may be sufficient for gene transfer in the genetic disease cystic fibrosis.

Indexed as

AdenoviridaeGenetic TherapyGenetic Vectors3T3 CellsAnimalsCell PolarityEpithelial CellsGlycosylphosphatidylinositolsHumansMiceReceptors, VirusRespiratory SystemTransfectionadenovirus receptorcoxsackievirus B receptorGlycosylphosphatidylinositolsReceptors, Virus

Identifiers

PMID11462042
PMCPMC115005
OpenAlexW2144198762

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.