Evidence map›Paper›PMID 30150645›Full record

ArticleNature structural & molecular biology2018

A dynamic three-step mechanism drives the HIV-1 pre-fusion reaction.

Maro Iliopoulou, Rory Nolan, Luis Alvarez, Yasunori Watanabe, Charles A Coomer, G Maria Jakobsdottir, Thomas A Bowden, Sergi Padilla-Parra

Erratum issuedAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

24 citing papers in PubMed, 39 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. HIV-1 Induced Cell-to-Cell Fusion or Syncytium Formation.Results and problems in cell differentiation · 2024
    Article
  5. Article
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  7. Article
  8. T Lymphocytes as Targets for SARS-CoV-2.Biochemistry. Biokhimiia · 2022
    Review
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  12. Review
  13. Article
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  15. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Maro IliopoulouCellular Imaging Core, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Rory NolanCellular Imaging Core, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Luis AlvarezCellular Imaging Core, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-1316-1906
Yasunori WatanabeDivision of Structural Biology, University of Oxford, Wellcome Trust Centre for Human Genetics, Oxford, UK.
Charles A CoomerCellular Imaging Core, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
G Maria JakobsdottirCellular Imaging Core, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Thomas A BowdenDivision of Structural Biology, University of Oxford, Wellcome Trust Centre for Human Genetics, Oxford, UK. tom@strubi.ox.ac.uk.ORCID http://orcid.org/0000-0002-8066-8785
Sergi Padilla-ParraCellular Imaging Core, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. spadilla@well.ox.ac.uk.ORCID http://orcid.org/0000-0002-8010-9481
Centre for Human Genetics · GBIkerbasque · ES

Funding

Medical Research Council MR/L009528/1Wellcome Trust 105278Wellcome Trust 203141Wellcome Trust 203852
6 · The paper itself

Abstract

Little is known about the intermolecular dynamics and stoichiometry of the interactions of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) protein with its receptors and co-receptors on the host cell surface. Here we analyze time-resolved HIV-1 Env interactions with T-cell surface glycoprotein CD4 (CD4) and C-C chemokine receptor type 5 (CCR5) or C-X-C chemokine receptor type 4 (CXCR4) on the surface of cells, by combining multicolor super-resolution localization microscopy (direct stochastic optical reconstruction microscopy) with fluorescence fluctuation spectroscopy imaging. Utilizing the primary isolate JR-FL and laboratory HXB2 strains, we reveal the time-resolved stoichiometry of CD4 and CCR5 or CXCR4 in the pre-fusion complex with HIV-1 Env. The HIV-1 Env pre-fusion dynamics for both R5- and X4-tropic strains consists of a three-step mechanism, which seems to differ in stoichiometry. Analyses with the monoclonal HIV-1-neutralizing antibody b12 indicate that the mechanism of inhibition differs between JR-FL and HXB2 Env. The molecular insights obtained here identify assemblies of HIV-1 Env with receptors and co-receptors as potential novel targets for inhibitor design.

Indexed as

Membrane FusionAnimalsCD4 AntigensChlorocebus aethiopsCOS CellsHEK293 CellsHIV-1HumansMicroscopyReceptors, CCR5Receptors, CXCR4Spectrometry, FluorescenceViral Envelope ProteinsCCR5 protein, humanCD4 AntigensCXCR4 protein, humanReceptors, CCR5Receptors, CXCR4Viral Envelope Proteins

Identifiers

PMID30150645
PMCPMC7056357
OpenAlexW2888430446

What OpenQuestion holds

Textmetadata
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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.