Evidence map›Paper›PMID 24307588›Full record

ArticleJournal of virology2014

High-multiplicity HIV-1 infection and neutralizing antibody evasion mediated by the macrophage-T cell virological synapse.

Christopher J A Duncan, James P Williams, Torben Schiffner, Kathleen Gärtner, Christina Ochsenbauer, John Kappes, Rebecca A Russell, John Frater, Quentin J Sattentau

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 1 pooled it
5.0field-weighted citation impact, top 4% 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

88 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.

  1. Pooled it
  2. Trial
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  5. Review
  6. Review
  7. Article
  8. Article
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  10. Article
  11. Role of Monocyte/Macrophages in the Pathogenesis of NeuroHIV.Results and problems in cell differentiation · 2024
    Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Type I interferon receptor (Frontiers in immunology · 2022
    Article
  17. Article
  18. Review
  19. Article
  20. Article

28 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 2 institutions in 2 countries.

Christopher J A DuncanSir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
James P Williams
Torben Schiffner
Kathleen Gärtner
Christina Ochsenbauer
John Kappes
Rebecca A Russell
John Frater
Quentin J Sattentau
University of Oxford · GBUniversity of Alabama at Birmingham · US

Funding

Virology CoreP30AI027767 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI OLAF KUTSCH · 1988 to 2026
$84.1M
Viral and Host Determinants of HIV-1 TransmissionU01AI067854 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F · 2005 to 2005
$14.9M
Medical Research Council G0000635Medical Research Council G0400453Medical Research Council G0901732Medical Research Council G108/626Medical Research Council MR/L006588/1NIAID NIH HHS P30 AI027767NIAID NIH HHS U01 AI067854NIAID NIH HHS UO1-AI067854Wellcome Trust 091911Wellcome Trust 094449/Z/10/Z
6 · The paper itself

Abstract

Macrophage infection is considered to play an important role in HIV-1 pathogenesis and persistence. Using a primary cell-based coculture model, we show that monocyte-derived macrophages (MDM) efficiently transmit a high-multiplicity HIV-1 infection to autologous CD4(+) T cells through a viral envelope glycoprotein (Env) receptor- and actin-dependent virological synapse (VS), facilitated by interactions between ICAM-1 and LFA-1. Virological synapse (VS)-mediated transmission by MDM results in high levels of T cell HIV-1 integration and is 1 to 2 orders of magnitude more efficient than cell-free infection. This mode of cell-to-cell transmission is broadly susceptible to the activity of CD4 binding site (CD4bs) and glycan or glycopeptide epitope-specific broadly neutralizing monoclonal antibodies (bNMAbs) but shows resistance to bNMAbs targeting the Env gp41 subunit membrane-proximal external region (MPER). These data define for the first time the structure and function of the macrophage-to-T cell VS and have important implications for bNMAb activity in HIV-1 prophylaxis and therapy. IMPORTANCE The ability of HIV-1 to move directly between contacting immune cells allows efficient viral dissemination with the potential to evade antibody attack. Here, we show that HIV-1 spreads from infected macrophages to T cells via a structure called a virological synapse that maintains extended contact between the two cell types, allowing transfer of multiple infectious events to the T cell. This process allows the virus to avoid neutralization by a class of antibody targeting the gp41 subunit of the envelope glycoproteins. These results have implications for viral spread in vivo and the specificities of neutralizing antibody elicited by antibody-based vaccines.

Indexed as

Analysis of VarianceAntibodies, MonoclonalAntibodies, NeutralizingCD4 AntigensCD4-Positive T-LymphocytesDNA PrimersHIV Envelope Protein gp41HIV InfectionsImmune EvasionImmunological SynapsesIntercellular Adhesion Molecule-1LuciferasesLymphocyte Function-Associated Antigen-1MacrophagesMicroscopy, ConfocalNeutralization TestsAntibodies, MonoclonalAntibodies, NeutralizingCD4 AntigensDNA PrimersHIV Envelope Protein gp41Intercellular Adhesion Molecule-1LuciferasesLymphocyte Function-Associated Antigen-1

Identifiers

PMID24307588
PMCPMC3911534
OpenAlexW2101835696

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.