Evidence map›Paper›PMID 33811831›Full record

ArticleCell host & microbe2021

The SMC5/6 complex compacts and silences unintegrated HIV-1 DNA and is antagonized by Vpr.

Liane Dupont, Stuart Bloor, James C Williamson, Sergio Martínez Cuesta, Raven Shah, Ana Teixeira-Silva, Adi Naamati, Edward J D Greenwood, Stefan G Sarafianos, Nicholas J Matheson and 1 more

Abstract read
In one paragraph

Article in Cell host & microbe, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing 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

61 citing papers in PubMed.

  1. Manipulation of the cell cycle by HIV-1.Biochemical Society transactions · 2026
    Review
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Chromatin Control of EBV Infection and Latency.Current topics in microbiology and immunology · 2025
    Article
  9. Article
  10. Article
  11. Unintegrated HIV-1 DNA recruits cGAS via its histone-binding domain to escape innate immunity.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. Review

1 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

11 authors.

Liane DupontCambridge Institute for Therapeutic Immunology & Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0AW, UK.
Stuart BloorCambridge Institute for Therapeutic Immunology & Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0AW, UK.
James C WilliamsonCambridge Institute for Therapeutic Immunology & Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0AW, UK.
Sergio Martínez CuestaCancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge CB2 0RE, UK.
Raven ShahLaboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.
Ana Teixeira-SilvaCambridge Institute for Therapeutic Immunology & Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0AW, UK.
Adi NaamatiCambridge Institute for Therapeutic Immunology & Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0AW, UK.
Edward J D GreenwoodCambridge Institute for Therapeutic Immunology & Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0AW, UK.
Stefan G SarafianosLaboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.
Nicholas J MathesonCambridge Institute for Therapeutic Immunology & Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0AW, UK.
Paul J LehnerCambridge Institute for Therapeutic Immunology & Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0AW, UK. Electronic address: pjl30@cam.ac.uk.

Funding

X-ray Crystallographic Fragment Screening CoreU54AI150472 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI SARAFIANOS, STEFAN G · 2019 to 2021
$15.7M
Structural studies of HIV Capsid with host factors and Capsid-targeting antiviralsR01AI120860 · NIAID · UNIVERSITY OF MISSOURI-COLUMBIA · PI Stefan G Sarafianos, Zhengqiang Wang · 2015 to 2026
$6.0M
Novel mechanism of integrase (IN) resistance to Dolutegravir through epistatic interactions between IN and the nucleocapsid and polypurine tract regions of HIV-1R01AI146017 · NIAID · EMORY UNIVERSITY · PI HACHIYA, ATSUKO, LYUMKIS, DMITRY · 2019 to 2023
$2.6M
Medical Research Council MR/P008801/1NIAID NIH HHS R01 AI120860NIAID NIH HHS R01 AI146017NIAID NIH HHS U54 AI150472Wellcome Trust 210688/Z/18/Z
6 · The paper itself

Abstract

Silencing of nuclear DNA is an essential feature of innate immune responses to invading pathogens. Early in infection, unintegrated lentiviral cDNA accumulates in the nucleus yet remains poorly expressed. In HIV-1-like lentiviruses, the Vpr accessory protein enhances unintegrated viral DNA expression, suggesting Vpr antagonizes cellular restriction. We previously showed how Vpr remodels the host proteome, identifying multiple cellular targets. We now screen these using a targeted CRISPR-Cas9 library and identify SMC5-SMC6 complex localization factor 2 (SLF2) as the Vpr target responsible for silencing unintegrated HIV-1. SLF2 recruits the SMC5/6 complex to unintegrated lentiviruses, and depletion of SLF2, or the SMC5/6 complex, increases viral expression. ATAC-seq demonstrates that Vpr-mediated SLF2 depletion increases chromatin accessibility of unintegrated virus, suggesting that the SMC5/6 complex compacts viral chromatin to silence gene expression. This work implicates the SMC5/6 complex in nuclear immunosurveillance of extrachromosomal DNA and defines its targeting by Vpr as an evolutionarily conserved antagonism.

Indexed as

Cell Cycle ProteinsChromosomal Proteins, Non-HistoneHIV-1HIV InfectionsHost-Pathogen InteractionsHumansReceptors, Interleukin-17Ubiquitin-Protein LigasesVirus IntegrationVirus Replicationvpr Gene Products, Human Immunodeficiency VirusCell Cycle ProteinsChromosomal Proteins, Non-HistoneIL17RB protein, humanReceptors, Interleukin-17SMC5 protein, humanSMC6 protein, humanUbiquitin-Protein Ligasesvpr Gene Products, Human Immunodeficiency VirusATAC-seqchromatin compactionCRISPR-Cas9 knockout screenExtrachromosomal DNAHIV-1SLF2SMC5-SMC6 complexunintegrated lentivirusviral gene silencingVpr

Identifiers

PMID33811831
PMCPMC8118623

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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.