Evidence map›Paper›PMID 21483486›Full record

ArticlePLoS pathogens2011

Dissection of the influenza A virus endocytic routes reveals macropinocytosis as an alternative entry pathway.

Erik de Vries, Donna M Tscherne, Marleen J Wienholts, Viviana Cobos-Jiménez, Florine Scholte, Adolfo García-Sastre, Peter J M Rottier, Cornelis A M de Haan

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 216 papers.

0numbers the graph read from it
0cells of the map it votes in
216citing papers in PubMed
10.2field-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

216 citing papers in PubMed, 333 citations in OpenAlex.

  1. Article
  2. Substitutions affecting the HA-NA-receptor balance preceded the emergence of the pandemic 2009 H1N1 virus.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  9. Update on the Efficacy of Vaccination on Host Immunity to Influenza Virus Infection.International archives of allergy and immunology · 2026
    Review
  10. Article
  11. Article
  12. Enhanced visualization of influenza A virus entry into living cells using virus-view atomic force microscopy.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Macropinosomes are a site of HIV-1 entry into primary CD4Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  20. Article

156 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

8 authors at 2 institutions in 2 countries.

Erik de VriesVirology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Donna M Tscherne
Marleen J Wienholts
Viviana Cobos-Jiménez
Florine Scholte
Adolfo García-Sastre
Peter J M Rottier
Cornelis A M de Haan
Utrecht University · NLIcahn School of Medicine at Mount Sinai · US

Funding

Novel role of 1918 influenza virus neuraminidase in hemagglutnin activationF32AI081428 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI TSCHERNE, DONNA · 2009 to 2010
$57k
NIAID NIH HHS 1F32AI081428NIAID NIH HHS F32 AI081428NIAID NIH HHS HHSN266200700010CNIAID NIH HHS U01 AI1074539
6 · The paper itself

Abstract

Influenza A virus (IAV) enters host cells upon binding of its hemagglutinin glycoprotein to sialylated host cell receptors. Whereas dynamin-dependent, clathrin-mediated endocytosis (CME) is generally considered as the IAV infection pathway, some observations suggest the occurrence of an as yet uncharacterized alternative entry route. By manipulating entry parameters we established experimental conditions that allow the separate analysis of dynamin-dependent and -independent entry of IAV. Whereas entry of IAV in phosphate-buffered saline could be completely inhibited by dynasore, a specific inhibitor of dynamin, a dynasore-insensitive entry pathway became functional in the presence of fetal calf serum. This finding was confirmed with the use of small interfering RNAs targeting dynamin-2. In the presence of serum, both IAV entry pathways were operational. Under these conditions entry could be fully blocked by combined treatment with dynasore and the amiloride derivative EIPA, the hallmark inhibitor of macropinocytosis, whereas either drug alone had no effect. The sensitivity of the dynamin-independent entry pathway to inhibitors or dominant-negative mutants affecting actomyosin dynamics as well as to a number of specific inhibitors of growth factor receptor tyrosine kinases and downstream effectors thereof all point to the involvement of macropinocytosis in IAV entry. Consistently, IAV particles and soluble FITC-dextran were shown to co-localize in cells in the same vesicles. Thus, in addition to the classical dynamin-dependent, clathrin-mediated endocytosis pathway, IAV enters host cells by a dynamin-independent route that has all the characteristics of macropinocytosis.

Indexed as

EndocytosisPinocytosisVirus InternalizationActomyosinAmilorideCell Line, TumorClathrinDynaminsFetal BloodGene SilencingHeLa CellsHost-Pathogen InteractionsHumansHydrazonesInfluenza A virusReceptor Protein-Tyrosine KinasesActomyosinAmilorideClathrinDynaminsethylisopropylamilorideHydrazonesN'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazideReceptor Protein-Tyrosine KinasesRNA, Small Interfering

Identifiers

PMID21483486
PMCPMC3068995
OpenAlexW2027816633

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.