Evidence map›Paper›PMID 16284249›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2005

Parvoviral virions deploy a capsid-tethered lipolytic enzyme to breach the endosomal membrane during cell entry.

Glen A Farr, Li-guo Zhang, Peter Tattersall

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed
4.4field-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

106 citing papers in PubMed, 187 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. The Journal of general virology · 2025
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Maturation of Viruses.Sub-cellular biochemistry · 2024
    Review
  12. Article
  13. Cryo-EM structure of adeno-associated virus 4 at 2.2 Å resolution.Acta crystallographica. Section D, Structural biology · 2023
    Article
  14. Nuclear entry and egress of parvoviruses.Molecular microbiology · 2022
    Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

46 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

3 authors at 2 institutions in 1 country.

Glen A FarrDepartment of Laboratory Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
Li-guo Zhang
Peter Tattersall
University of Florida · USYale University · US

Funding

MOLECULAR BASIS OF PARVOVIRUS TARGET CELL SPECIFICITYR01CA029303 · NCI · YALE UNIVERSITY · PI TATTERSALL, PETER J. · 1985 to 2016
$7.5M
PREDOCTORAL TRAINING PROGRAM IN MICROBIAL PATHOGENESIST32AI007640 · NIAID · YALE UNIVERSITY · PI GOODMAN, ANDREW L · 2000 to 2022
$4.3M
NCI NIH HHS CA 29303NCI NIH HHS R01 CA029303NIAID NIH HHS T32 AI 07640
6 · The paper itself

Abstract

Enveloped viruses deliver their virions into the host cell by fusion with the cellular plasma or endosomal membrane, thus creating topological continuity between the cytosol and the inside of the viral envelope. Nonenveloped viruses are, by their very nature, denied this strategy and must employ alternative methods to breach their host cell's delimiting membrane. We show here that the compact icosahedral parvoviral virion gains entry by deploying a lipolytic enzyme, phospholipase A(2) (PLA(2)), that is expressed at the N terminus of VP1, the minor coat protein. This region of VP1 is normally sequestered within the viral shell but is extruded during the entry process as a capsid-tethered domain. A single amino acid substitution in the active site of the VP1 PLA(2) inactivates enzymatic activity and abrogates infectivity. We have used transencapsidation of a vector expressing green fluorescent protein to show that infection by this PLA(2)-defective mutant can be complemented by coinfection with wild-type or mutant full virions, provided they can express a functional PLA(2). Even though wild-type empty capsids contain an active form of the enzyme, it is not externalized under physiological conditions, and such capsids are not able to complement the PLA(2) mutant. Significantly, highly efficient rescue can be achieved by polyethyleneimine-induced endosome rupture or by coinfection with adenovirus as long as uptake of the two viruses is simultaneous and the adenovirus is capable of deploying pVI, a capsid protein with endosomolytic activity. Together, these results demonstrate a previously unrecognized enzymatic mechanism for nonenveloped virus penetration.

Indexed as

Amino Acid SequenceAmino Acid SubstitutionAnimalsBase SequenceCapsid ProteinsCell LineEndosomesHistidineIntracellular MembranesLipolysisMiceMinute Virus of MiceMolecular Sequence DataPhospholipases AVirionCapsid ProteinsHistidinePhospholipases A

Identifiers

PMID16284249
PMCPMC1288001
OpenAlexW2044243584

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.