Evidence map›Paper›PMID 34260280›Full record

ArticleJournal of virology2021

Adeno-associated Virus 9 Structural Rearrangements Induced by Endosomal Trafficking pH and Glycan Attachment.

Judit J Penzes, Paul Chipman, Nilakshee Bhattacharya, Allison Zeher, Rick Huang, Robert McKenna, Mavis Agbandje-McKenna

Abstract read
In one paragraph

Article in Journal of virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
–field-weighted citation impact
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

40 citing papers in PubMed.

  1. Article
  2. Article
  3. Structural basis of liver de-targeting and neuronal tropism of CNS-targeted AAV capsids.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. In vivo selection in non-human primates identifies AAV capsids for on-target CSF delivery to spinal cord.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  20. Review
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.

Judit J PenzesDepartment of Biochemistry & Molecular Biology, Center for Structural Biology, The McKnight Brain Institute, College of Medicine, University of Floridagrid.15276.37, Gainesville, Florida, USA.ORCID 0000-0002-0366-9004
Paul ChipmanDepartment of Biochemistry & Molecular Biology, Center for Structural Biology, The McKnight Brain Institute, College of Medicine, University of Floridagrid.15276.37, Gainesville, Florida, USA.
Nilakshee BhattacharyaInstitute of Molecular Biophysics, Florida State Universitygrid.255986.5, Tallahassee, Florida, USA.
Allison ZeherLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
Rick HuangLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
Robert McKennaDepartment of Biochemistry & Molecular Biology, Center for Structural Biology, The McKnight Brain Institute, College of Medicine, University of Floridagrid.15276.37, Gainesville, Florida, USA.ORCID 0000-0002-2792-935X
Mavis Agbandje-McKennaDepartment of Biochemistry & Molecular Biology, Center for Structural Biology, The McKnight Brain Institute, College of Medicine, University of Floridagrid.15276.37, Gainesville, Florida, USA.ORCID 0000-0003-0565-5578

Funding

Structural studies of AAV capsids and their glycan receptor interactionsR01GM082946 · NIGMS · UNIVERSITY OF FLORIDA · PI ROBERT MCKENNA · 2007 to 2026
$6.1M
The Southeastern Consortium for Microscopy of MacroMolecular MachinesU24GM116788 · NIGMS · FLORIDA STATE UNIVERSITY · PI AGBANDJE-MCKENNA, MAVIS, BULLITT, ESTHER · 2016 to 2020
$4.6M
Purchase of a FEI Titan Krios for 3-D EMS10RR025080 · NCRR · FLORIDA STATE UNIVERSITY · PI TAYLOR, KENNETH ALLEN · 2008 to 2008
$2.0M
The role of pH and protease activity in AAV viral transductionR01GM109524 · NIGMS · UNIVERSITY OF FLORIDA · PI AGBANDJE-MCKENNA, MAVIS, MCKENNA, ROBERT · 2014 to 2017
$2.0M
Purchase of a direct electron camera for the Titan-Krios at FSUS10OD018142 · OD · FLORIDA STATE UNIVERSITY · PI TAYLOR, KENNETH ALLEN · 2014 to 2014
$384k
HHS | National Institutes of Health (NIH) S10 OD018142-01HHS | National Institutes of Health (NIH) S10 RR025080-01NCRR NIH HHS S10 RR025080NIGMS NIH HHS R01 GM082946NIGMS NIH HHS R01 GM109524NIGMS NIH HHS U24 GM116788NIH HHS S10 OD018142
6 · The paper itself

Abstract

Adeno-associated viruses (AAVs) are small nonenveloped single-stranded DNA (ssDNA) viruses that are currently being developed as gene therapy biologics. After cell entry, AAVs traffic to the nucleus using the endo-lysosomal pathway. The subsequent decrease in pH triggers conformational changes to the capsid that enable the externalization of the capsid protein (VP) N termini, including the unique domain of the minor capsid protein VP1 (VP1u), which permits the phospholipase activity required for the capsid lysosomal egress. Here, we report the AAV9 capsid structure, determined at the endosomal pHs (7.4, 6.0, 5.5, and 4.0), and terminal galactose-bound AAV9 capsids at pHs 7.4 and 5.5 using cryo-electron microscopy and three-dimensional image reconstruction. Taken together, these studies provide insight into AAV9 capsid conformational changes at the 5-fold pore during endosomal trafficking, in both the presence and absence of its cellular glycan receptor. We visualized, for the first time, that acidification induces the externalization of the VP3 and possibly VP2 N termini, presumably in prelude to the externalization of VP1u at pH 4.0, which is essential for lysosomal membrane disruption. In addition, the structural study of AAV9-galactose interactions demonstrates that AAV9 remains attached to its glycan receptor at the late endosome pH 5.5. This interaction significantly alters the conformational stability of the variable region I of the VPs, as well as the dynamics associated with VP N terminus externalization.

Indexed as

AcetylgalactosamineCapsidCapsid ProteinsCryoelectron MicroscopyDependovirusEndosomesGalactoseHydrogen-Ion ConcentrationImage Processing, Computer-AssistedModels, MolecularPolysaccharidesProtein ConformationProtein FoldingReceptors, VirusAcetylgalactosamineCapsid ProteinsGalactosePolysaccharidesReceptors, VirusAAV9adeno-associated viruscryoEMendosomal traffickinggene therapyglycan attachmentparvovirusreceptorsstructural virologyvesicular trafficking

Identifiers

PMID34260280
PMCPMC8428384

What OpenQuestion holds

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Registered trials

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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.