Evidence map›Paper›PMID 29610346›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2018

Flavivirus internalization is regulated by a size-dependent endocytic pathway.

Brent A Hackett, Sara Cherry

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
16.1field-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

74 citing papers in PubMed, 116 citations in OpenAlex.

  1. Dengue virus infection.Nature reviews. Disease primers · 2026
    Review
  2. Article
  3. Innate Immune and Inflammatory Responses to Dengue Virus Infection.Current topics in microbiology and immunology · 2026
    Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Zika Virus Neuropathogenesis-Research and Understanding.Pathogens (Basel, Switzerland) · 2024
    Review
  17. Insects · 2024
    Article
  18. Article
  19. Review
  20. Article

14 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

2 authors at 1 institution in 1 country.

Brent A HackettDepartment of Microbiology, University of Pennsylvania, Philadelphia, PA 19104.
Sara CherryDepartment of Microbiology, University of Pennsylvania, Philadelphia, PA 19104 cherrys@pennmedicine.upenn.edu.
University of Pennsylvania · US

Funding

TRAINING IN VIROLOGYT32AI007324 · NIAID · WISTAR INSTITUTE · PI Paul Bates, Matthew D. Weitzman · 1989 to 2026
$6.8M
The role of autophagy in innate anti-viral immunity in DrosophilaR01AI074951 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI CHERRY, SARA · 2007 to 2017
$4.2M
Antiviral immunity in the gut: how the intestinal epithelium and microbiota regulate infectionR01AI122749 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI CHERRY, SARA · 2016 to 2020
$2.0M
Dissecting the alphavirus entry receptor NRAMPR01AI095500 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI CHERRY, SARA · 2012 to 2015
$1.9M
NIAID NIH HHS R01 AI074951NIAID NIH HHS R01 AI095500NIAID NIH HHS R01 AI122749NIAID NIH HHS T32 AI007324
6 · The paper itself

Abstract

Flaviviruses enter host cells through the process of clathrin-mediated endocytosis, and the spectrum of host factors required for this process are incompletely understood. Here we found that lymphocyte antigen 6 locus E (LY6E) promotes the internalization of multiple flaviviruses, including West Nile virus, Zika virus, and dengue virus. Perhaps surprisingly, LY6E is dispensable for the internalization of the endogenous cargo transferrin, which is also dependent on clathrin-mediated endocytosis for uptake. Since viruses are substantially larger than transferrin, we reasoned that LY6E may be required for uptake of larger cargoes and tested this using transferrin-coated beads of similar size as flaviviruses. LY6E was indeed required for the internalization of transferrin-coated beads, suggesting that LY6E is selectively required for large cargo. Cell biological studies found that LY6E forms tubules upon viral infection and bead internalization, and we found that tubule formation was dependent on RNASEK, which is also required for flavivirus internalization, but not transferrin uptake. Indeed, we found that RNASEK is also required for the internalization of transferrin-coated beads, suggesting it functions upstream of LY6E. These LY6E tubules resembled microtubules, and we found that microtubule assembly was required for their formation and flavivirus uptake. Since microtubule end-binding proteins link microtubules to downstream activities, we screened the three end-binding proteins and found that EB3 promotes virus uptake and LY6E tubularization. Taken together, these results highlight a specialized pathway required for the uptake of large clathrin-dependent endocytosis cargoes, including flaviviruses.

Indexed as

Virus InternalizationAntigens, SurfaceCell Line, TumorDengue VirusEndocytosisEndoribonucleasesEthersFlavivirusGene Knockdown TechniquesGPI-Linked ProteinsHumansMicrospheresMicrotubule-Associated ProteinsMicrotubulesNocodazoleSpiro CompoundsAntigens, SurfaceEndoribonucleasesEthersGPI-Linked ProteinsLY6E protein, humanMAPRE3 protein, humanMicrotubule-Associated ProteinsnanchangmycinNocodazoleribonuclease KSpiro CompoundsTransferrinendocytosisentryflavivirusLY6Evirus

Identifiers

PMID29610346
PMCPMC5910848
OpenAlexW2795784950

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.