Evidence map›Paper›PMID 23427155›Full record

ArticleJournal of virology2013

Structure and dynamics of adeno-associated virus serotype 1 VP1-unique N-terminal domain and its role in capsid trafficking.

Balasubramanian Venkatakrishnan, Joseph Yarbrough, John Domsic, Antonette Bennett, Brian Bothner, Olga G Kozyreva, R Jude Samulski, Nicholas Muzyczka, Robert McKenna, Mavis Agbandje-McKenna

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.

0numbers the graph read from it
0cells of the map it votes in
142citing papers in PubMed
5.8field-weighted citation impact, top 4% 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

142 citing papers in PubMed, 218 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Immunogenicity of Gene and Cell Therapies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  11. Article
  12. Article
  13. Review
  14. The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025
    Review
  15. Article
  16. Article
  17. pH-dependent DNA degradation pathways for adeno-associated virus gene therapy.Molecular therapy. Methods & clinical development · 2025
    Article
  18. Article
  19. Article
  20. Article

82 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

10 authors at 3 institutions in 1 country.

Balasubramanian VenkatakrishnanDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, Florida, USA.
Joseph Yarbrough
John Domsic
Antonette Bennett
Brian Bothner
Olga G Kozyreva
R Jude Samulski
Nicholas Muzyczka
Robert McKenna
Mavis Agbandje-McKenna
University of Florida · USUniversity of North Carolina at Chapel Hill · USMontana State University · US

Funding

VIRAL VECTOR DELIVERY OF ANTISENSE TO ACE MRNA IN CARDIOVASCULAR DISEASEP01HL059412 · NHLBI · UNIVERSITY OF FLORIDA · PI MUZYCZKA, NICHOLAS · 1998 to 2012
$20.2M
Structural studies of AAV capsids and their glycan receptor interactionsR01GM082946 · NIGMS · UNIVERSITY OF FLORIDA · PI ROBERT MCKENNA · 2007 to 2026
$6.1M
Rational and Combinatorial Engineering of AAV VectorsR01AI072176 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HIRSCH, MATTHEW LOUIS, SAMULSKI, RICHARD J · 2008 to 2017
$3.7M
Mapping Adeno-associated Virus Capsid Structural and Dynamic TransitionsR01AI081961 · NIAID · MONTANA STATE UNIVERSITY - BOZEMAN · PI BOTHNER, BRIAN P · 2009 to 2012
$1.4M
NHLBI NIH HHS P01 HL059412NHLBI NIH HHS P01 HL59412NIAID NIH HHS R01 AI072176NIAID NIH HHS R01 AI081961NIGMS NIH HHS R01 GM082946
6 · The paper itself

Abstract

The importance of the phospholipase A2 domain located within the unique N terminus of the capsid viral protein VP1 (VP1u) in parvovirus infection has been reported. This study used computational methods to characterize the VP1 sequence for adeno-associated virus (AAV) serotypes 1 to 12 and circular dichroism and electron microscopy to monitor conformational changes in the AAV1 capsid induced by temperature and the pHs encountered during trafficking through the endocytic pathway. Circular dichroism was also used to monitor conformational changes in AAV6 capsids assembled from VP2 and VP3 or VP1, VP2, and VP3 at pH 7.5. VP1u was predicted (computationally) and confirmed (in solution) to be structurally ordered. This VP domain was observed to undergo a reversible pH-induced unfolding/refolding process, a loss/gain of α-helical structure, which did not disrupt the capsid integrity and is likely facilitated by its difference in isoelectric point compared to the other VP sequences assembling the capsid. This study is the first to physically document conformational changes in the VP1u region that likely facilitate its externalization from the capsid interior during infection and establishes the order of events in the escape of the AAV capsid from the endosome en route to the nucleus.

Indexed as

CapsidCapsid ProteinsCircular DichroismDependovirusMicroscopy, ElectronModels, MolecularProtein Structure, TertiaryProtein TransportVirus AssemblyCapsid Proteins

Identifiers

PMID23427155
PMCPMC3624325
OpenAlexW1969538192

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.