Evidence map›Paper›PMID 33462517›Full record

ArticleNature structural & molecular biology2021

Ebola virus glycoprotein interacts with cholesterol to enhance membrane fusion and cell entry.

Jinwoo Lee, Alex J B Kreutzberger, Laura Odongo, Elizabeth A Nelson, David A Nyenhuis, Volker Kiessling, Binyong Liang, David S Cafiso, Judith M White, Lukas K Tamm

Open access · greenAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.3field-weighted citation impact, top 6% 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

33 citing papers in PubMed, 58 citations in OpenAlex.

  1. Article
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  3. Review
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  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Inconspicuous Yet Indispensable: The Coronavirus Spike Transmembrane Domain.International journal of molecular sciences · 2023
    Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. The Art of Viral Membrane Fusion and Penetration.Sub-cellular biochemistry · 2023
    Article
  20. Lipid and Lipidation in Membrane Fusion.The Journal of membrane biology · 2022
    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

10 authors at 1 institution in 1 country.

Jinwoo LeeCenter for Membrane and Cell Physiology, University of Virginia, Charlottesville, VA, USA.
Alex J B KreutzbergerCenter for Membrane and Cell Physiology, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0002-9774-115X
Laura OdongoCenter for Membrane and Cell Physiology, University of Virginia, Charlottesville, VA, USA.
Elizabeth A NelsonCenter for Membrane and Cell Physiology, University of Virginia, Charlottesville, VA, USA.
David A NyenhuisCenter for Membrane and Cell Physiology, University of Virginia, Charlottesville, VA, USA.
Volker KiesslingCenter for Membrane and Cell Physiology, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0002-9388-5703
Binyong LiangCenter for Membrane and Cell Physiology, University of Virginia, Charlottesville, VA, USA.
David S CafisoCenter for Membrane and Cell Physiology, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0002-3813-8721
Judith M WhiteCenter for Membrane and Cell Physiology, University of Virginia, Charlottesville, VA, USA.
Lukas K TammCenter for Membrane and Cell Physiology, University of Virginia, Charlottesville, VA, USA. lkt2e@virginia.edu.ORCID http://orcid.org/0000-0002-1674-4464
University of Virginia · US

Funding

VIRAL SPIKE GLYCOPROTEIN-MEDIATED MEMBRANE POTENTIALR01AI030557 · NIAID · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI TAMM, LUKAS K · 1991 to 2022
$6.2M
MOLECULAR MECHANISMS OF VIRAL MEMBRANE FUSIONR37AI030557 · NIAID · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI TAMM, LUKAS K · 2003 to 2011
$3.4M
Training in Molecular BiophysicsT32GM080186 · NIGMS · UNIVERSITY OF VIRGINIA · PI NAKAMOTO, ROBERT K. · 2008 to 2019
$1.5M
Combinations of Approved Drugs to Combat Ebola VirusR01AI114776 · NIAID · UNIVERSITY OF VIRGINIA · PI WHITE, JUDITH M. · 2015 to 2017
$1.5M
Upgrade of Bruker EPR SpectrometerS10OD025149 · OD · UNIVERSITY OF VIRGINIA · PI CAFISO, DAVID S · 2018 to 2018
$396k
NIAID NIH HHS R01 AI030557NIAID NIH HHS R01 AI114776NIAID NIH HHS R37 AI030557NIGMS NIH HHS T32 GM080186NIH HHS S10 OD025149
6 · The paper itself

Abstract

Cholesterol serves critical roles in enveloped virus fusion by modulating membrane properties. The glycoprotein (GP) of Ebola virus (EBOV) promotes fusion in the endosome, a process that requires the endosomal cholesterol transporter NPC1. However, the role of cholesterol in EBOV fusion is unclear. Here we show that cholesterol in GP-containing membranes enhances fusion and the membrane-proximal external region and transmembrane (MPER/TM) domain of GP interacts with cholesterol via several glycine residues in the GP2 TM domain, notably G660. Compared to wild-type (WT) counterparts, a G660L mutation caused a more open angle between MPER and TM domains in an MPER/TM construct, higher probability of stalling at hemifusion for GP2 proteoliposomes and lower cell entry of virus-like particles (VLPs). VLPs with depleted cholesterol show reduced cell entry, and VLPs produced under cholesterol-lowering statin conditions show less frequent entry than respective controls. We propose that cholesterol-TM interactions affect structural features of GP2, thereby facilitating fusion and cell entry.

Indexed as

Membrane FusionVirus InternalizationCholesterolEbolavirusHEK293 CellsHemorrhagic Fever, EbolaHumansProtein BindingProtein DomainsViral Envelope ProteinsCholesterolenvelope glycoprotein, Ebola virusViral Envelope Proteins

Identifiers

PMID33462517
PMCPMC7992113
OpenAlexW3124343464

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.