Evidence map›Paper›PMID 29203900›Full record

ArticleScientific reports2017

Intracellular immunization against HIV infection with an intracellular antibody that mimics HIV integrase binding to the cellular LEDGF protein.

Leyuan Bao, Clare Hannon, Abimael Cruz-Mignoni, Denis Ptchelkine, Mei-Yi Sun, Ami Miller, Wilawan Bunjobpol, Camilo E Quevedo, Mariliza Derveni, Jennifer Chambers and 3 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.0field-weighted citation impact, top 27% 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

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Applying Antibodies Inside Cells: Principles and Recent Advances in Neurobiology, Virology and Oncology.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2020
    Review
  4. Review
  5. Article
  6. 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

13 authors at 3 institutions in 1 country.

Leyuan BaoWeatherall Institute of Molecular Medicine, MRC Human Immunology Unit, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
Clare HannonSchool of Clinical Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Rd, Cambridge, CB2 0SP, UK.
Abimael Cruz-MignoniWeatherall Institute of Molecular Medicine, MRC Molecular Haematology Unit, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
Denis PtchelkineResearch Complex at Harwell, Rutherford Appleton Laboratory, Didcot, OX11 0FA, UK.ORCID 0000-0001-8821-3200
Mei-Yi SunWeatherall Institute of Molecular Medicine, MRC Human Immunology Unit, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
Ami MillerWeatherall Institute of Molecular Medicine, MRC Molecular Haematology Unit, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
Wilawan BunjobpolWeatherall Institute of Molecular Medicine, MRC Molecular Haematology Unit, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
Camilo E QuevedoWeatherall Institute of Molecular Medicine, MRC Molecular Haematology Unit, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
Mariliza DerveniWeatherall Institute of Molecular Medicine, MRC Molecular Haematology Unit, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
Jennifer ChambersWeatherall Institute of Molecular Medicine, MRC Molecular Haematology Unit, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
Alison SimmonsWeatherall Institute of Molecular Medicine, MRC Human Immunology Unit, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
Simon E V PhillipsResearch Complex at Harwell, Rutherford Appleton Laboratory, Didcot, OX11 0FA, UK.
Terence H RabbittsWeatherall Institute of Molecular Medicine, MRC Molecular Haematology Unit, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK. terence.rabbitts@imm.ox.ac.uk.
John Radcliffe Hospital · GBRutherford Appleton Laboratory · GBUniversity of Cambridge · GB

Funding

Department of Health NIHR-RP-R3-12-026Medical Research Council MC_UU_00008/7Medical Research Council MC_UU_00016/16Medical Research Council MC_UU_12010/7Medical Research Council MR/J000612/1Wellcome Trust 099246
6 · The paper itself

Abstract

Preventing the protein-protein interaction of the cellular chromatin binding protein Lens Epithelium-Derived Growth Factor (LEDGF) and human immunodeficiency virus (HIV) integrase is an important possible strategy for anti-viral treatment for AIDS. We have used Intracellular Antibody Capture technology to isolate a single VH antibody domain that binds to LEDGF. The crystal structure of the LEDGF-VH complex reveals that the single domain antibody mimics the effect of binding of HIV integrase to LEDGF which is crucial for HIV propagation. CD4-expressing T cell lines were constructed to constitutively express the LEDGF-binding VH and these cells showed interference with HIV viral replication, assayed by virus capsid protein p24 production. Therefore, pre-conditioning cells to express antibody fragments confers effective intracellular immunization for preventing chronic viral replication and can be a way to prevent HIV spread in infected patients. This raises the prospect that intracellular immunization strategies that focus on cellular components of viral integrase protein interactions can be used to combat the problems associated with latent HIV virus re-emergence in patients. New genome editing development, such as using CRISPR/cas9, offer the prospect intracellularly immunized T cells in HIV+ patients.

Indexed as

Amino Acid SequenceAnimalsBinding SitesCD4-Positive T-LymphocytesCrystallography, X-RayHIV Core Protein p24HIV InfectionsHIV IntegraseHumansIntercellular Signaling Peptides and ProteinsJurkat CellsMiceMolecular Dynamics SimulationProtein BindingSequence AlignmentSingle-Domain AntibodiesHIV Core Protein p24HIV IntegraseIntercellular Signaling Peptides and Proteinslens epithelium-derived growth factorSingle-Domain Antibodies

Identifiers

PMID29203900
PMCPMC5715112
OpenAlexW2770804584

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.