Evidence map›Paper›PMID 25157142›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Nonlytic viral spread enhanced by autophagy components.

Sara Whitney Bird, Nathaniel D Maynard, Markus W Covert, Karla Kirkegaard

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers.

0numbers the graph read from it
0cells of the map it votes in
173citing papers in PubMed
12.7field-weighted citation impact, top 1% 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

173 citing papers in PubMed, 249 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Serial passagingFrontiers in cellular and infection microbiology · 2026
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Journal of virology · 2025
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Non-lytic spread of poliovirus requires the nonstructural protein 3CD.bioRxiv : the preprint server for biology · 2024
    Article
  20. Article

113 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

4 authors at 1 institution in 1 country.

Sara Whitney BirdDepartments of Microbiology and Immunology and.
Nathaniel D MaynardBioengineering, Stanford University School of Medicine, Stanford, CA 94305.
Markus W CovertBioengineering, Stanford University School of Medicine, Stanford, CA 94305.
Karla KirkegaardDepartments of Microbiology and Immunology and karlak@stanford.edu.
Stanford University · US

Funding

Supplement to Enhance Wellness and Resiliency in the Graduate EnvironmentT32GM007276 · NIGMS · STANFORD UNIVERSITY · PI MORRISON, ASHBY J. · 1985 to 2023
$32.9M
MOLECULAR BASIS OF HOST-PARASITE INTERACTIONT32AI007328 · NIAID · STANFORD UNIVERSITY · PI JUSTIN L SONNENBURG · 1987 to 2026
$11.9M
TRAINING & OUTREACH COREP50GM107615 · NIGMS · STANFORD UNIVERSITY · PI FERRELL, JAMES E. · 2013 to 2017
$10.9M
NIH Director's Pioneer AwardDP1OD000827 · OD · STANFORD UNIVERSITY · PI KIRKEGAARD, KARLA · 2006 to 2010
$3.9M
Subversion of Autophagy Pathway and Constituents by RNA virusesR56AI103500 · NIAID · STANFORD UNIVERSITY · PI KIRKEGAARD, KARLA · 2013 to 2013
$466k
NIAID NIH HHS R56 AI103500NIAID NIH HHS T32 AI007328NIGMS NIH HHS P50 GM107615NIGMS NIH HHS T32 GM007276NIH HHS DP1 OD000827
6 · The paper itself

Abstract

The cell-to-cell spread of cytoplasmic constituents such as nonenveloped viruses and aggregated proteins is usually thought to require cell lysis. However, mechanisms of unconventional secretion have been described that bypass the secretory pathway for the extracellular delivery of cytoplasmic molecules. Components of the autophagy pathway, an intracellular recycling process, have been shown to play a role in the unconventional secretion of cytoplasmic signaling proteins. Poliovirus is a lytic virus, although a few examples of apparently nonlytic spread have been documented. Real demonstration of nonlytic spread for poliovirus or any other cytoplasmic constituent thought to exit cells via unconventional secretion requires demonstration that a small amount of cell lysis in the cellular population is not responsible for the release of cytosolic material. Here, we use quantitative time-lapse microscopy to show the spread of infectious cytoplasmic material between cells in the absence of lysis. siRNA-mediated depletion of autophagy protein LC3 reduced nonlytic intercellular viral transfer. Conversely, pharmacological stimulation of the autophagy pathway caused more rapid viral spread in tissue culture and greater pathogenicity in mice. Thus, the unconventional secretion of infectious material in the absence of cell lysis is enabled by components of the autophagy pathway. It is likely that other nonenveloped viruses also use this pathway for nonlytic intercellular spread to affect pathogenesis in infected hosts.

Indexed as

AutophagyAnimalsCell Line, TumorCell SurvivalHumansImaging, Three-DimensionalMiceMicrotubule-Associated ProteinsPoliomyelitisPoliovirusSingle-Cell AnalysisTissue Culture TechniquesMicrotubule-Associated Proteinslive imagingvirus spread

Identifiers

PMID25157142
PMCPMC4246951
OpenAlexW1979661536

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.