Evidence map›Paper›PMID 31042482›Full record

ArticleCell reports2019

Promiscuous Targeting of Cellular Proteins by Vpr Drives Systems-Level Proteomic Remodeling in HIV-1 Infection.

Edward J D Greenwood, James C Williamson, Agata Sienkiewicz, Adi Naamati, Nicholas J Matheson, Paul J Lehner

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
–field-weighted citation impact
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

67 citing papers in PubMed.

  1. Review
  2. Manipulation of the cell cycle by HIV-1.Biochemical Society transactions · 2026
    Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. HIV-1 Vif and Vpr cooperatively modulate the cell cycle to maximize per-cell virion production.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. Review

7 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

6 authors.

Edward J D GreenwoodDepartment of Medicine, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0QQ, UK; Cambridge Institute for Medical Research, Keith Peters Building, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0XY, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0AW, UK. Electronic address: ejdg2@cam.ac.uk.
James C WilliamsonDepartment of Medicine, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0QQ, UK; Cambridge Institute for Medical Research, Keith Peters Building, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0XY, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0AW, UK. Electronic address: jcw76@cam.ac.uk.
Agata SienkiewiczDepartment of Medicine, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0QQ, UK; Cambridge Institute for Medical Research, Keith Peters Building, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0XY, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0AW, UK.
Adi NaamatiDepartment of Medicine, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0QQ, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0AW, UK.
Nicholas J MathesonDepartment of Medicine, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0QQ, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0AW, UK.
Paul J LehnerDepartment of Medicine, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0QQ, UK; Cambridge Institute for Medical Research, Keith Peters Building, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0XY, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0AW, UK. Electronic address: pjl30@cam.ac.uk.

Funding

Department of HealthMedical Research Council MR/P008801/1Wellcome TrustWellcome Trust 210688/Z/18/Z
6 · The paper itself

Abstract

HIV-1 encodes four "accessory proteins" (Vif, Vpr, Vpu, and Nef), dispensable for viral replication in vitro but essential for viral pathogenesis in vivo. Well characterized cellular targets have been associated with Vif, Vpu, and Nef, which counteract host restriction and promote viral replication. Conversely, although several substrates of Vpr have been described, their biological significance remains unclear. Here, we use complementary unbiased mass spectrometry-based approaches to demonstrate that Vpr is both necessary and sufficient for the DCAF1/DDB1/CUL4 E3 ubiquitin ligase-mediated degradation of at least 38 cellular proteins, causing systems-level changes to the cellular proteome. We therefore propose that promiscuous targeting of multiple host factors underpins complex Vpr-dependent cellular phenotypes and validate this in the case of G2/M cell cycle arrest. Our model explains how Vpr modulates so many cell biological processes and why the functional consequences of previously described Vpr targets, identified and studied in isolation, have proved elusive.

Indexed as

Cell Line, TumorConserved SequenceG2 Phase Cell Cycle CheckpointsHEK293 CellsHIV-1HIV InfectionsHumansProteolysisProteomeUbiquitinationUbiquitin-Protein Ligasesvpr Gene Products, Human Immunodeficiency VirusProteomeUbiquitin-Protein Ligasesvpr Gene Products, Human Immunodeficiency VirusHIVIP-MSmass spectrometryproteomicspulsed SILACSIVTMTVprVpx

Identifiers

PMID31042482
PMCPMC6506760

What OpenQuestion holds

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Registered trials

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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.