Evidence map›Paper›PMID 27572837›Full record

ArticleNature microbiology2016

The hemifusion structure induced by influenza virus haemagglutinin is determined by physical properties of the target membranes.

Petr Chlanda, Elena Mekhedov, Hang Waters, Cindi L Schwartz, Elizabeth R Fischer, Rolf J Ryham, Fredric S Cohen, Paul S Blank, Joshua Zimmerberg

Abstract read
In one paragraph

Article in Nature microbiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed
7.3field-weighted citation impact, top 2% 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

84 citing papers in PubMed, 164 citations in OpenAlex.

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  10. SARS-CoV-2 FP1 Destabilizes Lipid Membranes and Facilitates Pore Formation.International journal of molecular sciences · 2025
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24 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

9 authors at 4 institutions in 1 country.

Petr ChlandaSection on Integrative Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA.
Elena MekhedovSection on Integrative Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA.
Hang WatersSection on Integrative Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA.
Cindi L SchwartzRocky Mountain Laboratories, Electron Microscopy Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton 59840, Montana, USA.
Elizabeth R FischerRocky Mountain Laboratories, Electron Microscopy Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton 59840, Montana, USA.
Rolf J RyhamDepartment of Mathematics, Fordham University, Bronx, New York 10458, USA.
Fredric S CohenDepartment of Molecular Biophysics and Physiology, Rush University, Chicago, Illinois 60612, USA.
Paul S BlankSection on Integrative Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA.
Joshua ZimmerbergSection on Integrative Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA.ORCID 0000-0002-1707-3789
Eunice Kennedy Shriver National Institute of Child Health and Human Development · USNational Institutes of Health · USFordham University · USRush University · US

Funding

Infectious Diseases Research Technologies Core - RMLZICAI001052 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CHERRY, JAMES · 2009 to 2025
$133.3M
Membrane Remodeling in Viral Infection, Parasite Replication, and Traumatic Brain InjuryZIAHD001409 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI ZIMMERBERG, JOSHUA · 2009 to 2025
$29.9M
Molecular Regulation of Fusion: Voltage Dependence and Local Physical InteractionR01GM101539 · NIGMS · RUSH UNIVERSITY MEDICAL CENTER · PI COHEN, FREDRIC S · 2013 to 2016
$1.4M
Intramural NIH HHS ZIA HD001409NIGMS NIH HHS R01 GM101539
6 · The paper itself

Abstract

Influenza A virus haemagglutinin conformational change drives the membrane fusion of viral and endosomal membranes at low pH. Membrane fusion proceeds through an intermediate called hemifusion(1,2). For viral fusion, the hemifusion structures are not determined(3). Here, influenza virus-like particles(4) carrying wild-type haemagglutinin or haemagglutinin hemifusion mutant G1S(5) and liposome mixtures were studied at low pH by Volta phase plate cryo-electron tomography, which improves the signal-to-noise ratio close to focus. We determined two distinct hemifusion structures: a hemifusion diaphragm and a novel structure termed a 'lipidic junction'. Liposomes with lipidic junctions were ruptured with membrane edges stabilized by haemagglutinin. The rupture frequency and hemifusion diaphragm diameter were not affected by G1S mutation, but decreased when the cholesterol level in the liposomes was close to physiological concentrations. We propose that haemagglutinin induces a merger between the viral and target membranes by one of two independent pathways: a rupture-insertion pathway leading to the lipidic junction and a hemifusion-stalk pathway leading to a fusion pore. The latter is relevant under the conditions of influenza virus infection of cells. Cholesterol concentration functions as a pathway switch because of its negative spontaneous curvature in the target bilayer, as determined by continuum analysis.

Indexed as

Membrane FusionCholesterolHemagglutinin Glycoproteins, Influenza VirusHydrogen-Ion ConcentrationLipid BilayersLiposomesMembranesMutationPhysical PhenomenaViral Fusion ProteinsCholesterolHemagglutinin Glycoproteins, Influenza Virushemagglutinin, human influenza A virusLipid BilayersLiposomesViral Fusion Proteins

Identifiers

PMID27572837
PMCPMC4876733
OpenAlexW2336704254

What OpenQuestion holds

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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.