Evidence map›Paper›PMID 29355500›Full record

ArticleJournal of molecular biology2018

Influenza Hemifusion Phenotype Depends on Membrane Context: Differences in Cell-Cell and Virus-Cell Fusion.

Katarzyna E Zawada, Kenta Okamoto, Peter M Kasson

Open access · bronzeAbstract read
In one paragraph

Article in Journal of molecular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

17 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. How Do Cancer Cells Fuse and Why?Advances in experimental medicine and biology · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. The Art of Viral Membrane Fusion and Penetration.Sub-cellular biochemistry · 2023
    Article
  8. Article
  9. Computational methods to study enveloped viral entry.Biochemical Society transactions · 2021
    Review
  10. Review
  11. Article
  12. Biochimica et biophysica acta. Biomembranes · 2020
    Article
  13. Influenza hemagglutinin drives viral entry via two sequential intramembrane mechanisms.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  14. Article
  15. Article
  16. Article
  17. Early Virus-Host Cell Interactions.Journal of molecular biology · 2018
    Article
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 3 institutions in 2 countries.

Katarzyna E ZawadaDepartment of Molecular Physiology and Biological Physics and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA.
Kenta OkamotoScience for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
Peter M KassonDepartment of Molecular Physiology and Biological Physics and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA; Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden. Electronic address: kasson@virginia.edu.
Science for Life Laboratory · SEUniversity of Virginia · USUppsala University · SE

Funding

Understanding fusion peptide mutations in influenza hemagglutininR01GM098304 · NIGMS · UNIVERSITY OF VIRGINIA · PI KASSON, PETER M · 2012 to 2016
$1.7M
NIGMS NIH HHS R01 GM098304
6 · The paper itself

Abstract

Influenza viral entry into the host cell cytoplasm is accomplished by a process of membrane fusion mediated by the viral hemagglutinin protein. Hemagglutinin acts in a pH-triggered fashion, inserting a short fusion peptide into the host membrane followed by refolding of a coiled-coil structure to draw the viral envelope and host membranes together. Mutations to this fusion peptide provide an important window into viral fusion mechanisms and protein-membrane interactions. Here, we show that a well-described fusion peptide mutant, G1S, has a phenotype that depends strongly on the viral membrane context. The G1S mutant is well known to cause a "hemifusion" phenotype based on experiments in transfected cells, where cells expressing G1S hemagglutinin can undergo lipid mixing in a pH-triggered fashion similar to virus but will not support fusion pores. We compare fusion by the G1S hemagglutinin mutant expressed either in cells or in influenza virions and show that this hemifusion phenotype occurs in transfected cells but that native virions are able to support full fusion, albeit at a slower rate and 10-100× reduced infectious titer. We explain this with a quantitative model where the G1S mutant, instead of causing an absolute block of fusion, alters the protein stoichiometry required for fusion. This change slightly slows fusion at high hemagglutinin density, as on the viral surface, but at lower hemagglutinin density produces a hemifusion phenotype. The quantitative model thus reproduces the observed virus-cell and cell-cell fusion phenotypes, yielding a unified explanation where membrane context can control the observed viral fusion phenotype.

Indexed as

Cell FusionMembrane FusionPhenotypeVirus InternalizationCell MembraneHemagglutinin Glycoproteins, Influenza VirusHemagglutininsHost-Pathogen InteractionsHumansHydrogen-Ion ConcentrationInfluenza A virusInfluenza, HumanMembranesOrthomyxoviridaeViral Fusion ProteinsVirionHemagglutinin Glycoproteins, Influenza VirusHemagglutininsViral Fusion Proteinsfusion peptidehemifusioninfluenza virusmembrane fusionstoichiometry

Identifiers

PMID29355500
PMCPMC5831491
OpenAlexW2793600706

What OpenQuestion holds

Textmetadata
LicenceTDM
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.