Evidence map›Paper›PMID 26536268›Full record

ArticleBiophysical journal2015

Hemagglutinin Spatial Distribution Shifts in Response to Cholesterol in the Influenza Viral Envelope.

Marta K Domanska, Rebecca A Dunning, Kelly A Dryden, Katarzyna E Zawada, Mark Yeager, Peter M Kasson

Open access · bronzeAbstract read
In one paragraph

Article in Biophysical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

15 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Good Cholesterol Gone Bad? HDL and COVID-19.International journal of molecular sciences · 2021
    Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Single-particle fusion of influenza viruses reveals complex interactions with target membranes.Journal of physics. Condensed matter : an Institute of Physics journal · 2018
    Article
  12. The role of cholesterol in membrane fusion.Chemistry and physics of lipids · 2016
    Review
  13. Article
  14. Article
  15. Review
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

6 authors at 1 institution in 1 country.

Marta K DomanskaMolecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia.
Rebecca A DunningMolecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia.
Kelly A DrydenMolecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia.
Katarzyna E ZawadaMolecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia.
Mark YeagerMolecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia.
Peter M KassonMolecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia. Electronic address: kasson@virginia.edu.
University of Virginia · US

Funding

INFECTIOUS DISEASES TRAINING PROGRAMT32AI007046 · NIAID · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Alison K Criss, William A Petri · 1985 to 2026
$15.3M
Structure Analysis of Viral Assembly MechanismsR01GM066087 · NIGMS · UNIVERSITY OF VIRGINIA · PI YEAGER, MARK JAY · 2003 to 2014
$4.4M
Global Biothreats Training ProgramT32AI055432 · NIAID · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI CRISS, ALISON K, PETRI, WILLIAM A · 2003 to 2022
$4.0M
Understanding fusion peptide mutations in influenza hemagglutininR01GM098304 · NIGMS · UNIVERSITY OF VIRGINIA · PI KASSON, PETER M · 2012 to 2016
$1.7M
NIAID NIH HHS T32 AI007046NIAID NIH HHS T32 AI055432NIGMS NIH HHS GM098304NIGMS NIH HHS R01-GM066076NIGMS NIH HHS R01 GM066087NIGMS NIH HHS R01 GM098304
6 · The paper itself

Abstract

Influenza virus delivers its genome to the host cytoplasm via a process of membrane fusion mediated by the viral hemagglutinin protein. Optimal fusion likely requires multiple hemagglutinin trimers, so the spatial distribution of hemagglutinin on the viral envelope may influence fusion mechanism. We have previously shown that moderate depletion of cholesterol from the influenza viral envelope accelerates fusion kinetics even though it decreases fusion efficiency, both in a reversible manner. Here, we use electron cryo-microscopy to measure how the hemagglutinin lateral density in the viral envelope changes with cholesterol extraction. We extract this information by measuring the radial distribution function of electron density in >4000 viral images per sample, assigning hemagglutinin density by comparing images with and without anti-HA Fab bound. On average, hemagglutinin trimers move closer together: we estimate that the typical trimer-trimer spacing reduces from 94 to 84 Å when ∼90% of cholesterol is removed from the viral membrane. Upon restoration of viral envelope cholesterol, this spacing once again expands. This finding can qualitatively explain the observed changes to fusion kinetics: contemporary models from single-virus microscopy are that fusion requires the engagement of several hemagglutinin trimers in close proximity. If removing cholesterol increases the lateral density of hemagglutinin, this should result in an increase in the rate of fusion.

Indexed as

AnimalsCholesterolCryoelectron MicroscopyDogsHemagglutininsMadin Darby Canine Kidney CellsOrthomyxoviridaeProtein MultimerizationViral Envelope ProteinsVirionCholesterolHemagglutininsViral Envelope Proteins

Identifiers

PMID26536268
PMCPMC4643271
OpenAlexW1936348222

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.