ArticleCell host & microbe2021
The SMC5/6 complex compacts and silences unintegrated HIV-1 DNA and is antagonized by Vpr.
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.
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Who cites it
61 citing papers in PubMed.
- Manipulation of the cell cycle by HIV-1.Biochemical Society transactions · 2026Review
- The Multifunctional SMC5/6 Complex in Genome Stability, Antiviral Restriction, and Human Disease.Current issues in molecular biology · 2026Review
- The HIV-1 restriction factor RPRD2 does not inhibit transcription of HIV-1 or endogenous retroelements.bioRxiv : the preprint server for biology · 2026Article
- Non-integrase mechanisms for dolutegravir resistance.Retrovirology · 2026Review
- Epigenetic mechanisms of retroviral regulation: a comparative review.Epigenetics & chromatin · 2026Review
- DNA damage induced by HIV-1 Vpr triggers epigenetic remodeling and transcriptional programs to enhance virus transcription and latency reactivation.PLoS biology · 2026Article
- SMC5/6-mediated plasmid silencing is directed by SIMC1-SLF2 and antagonized by the SV40 large T antigen.eLife · 2025Article
- Chromatin Control of EBV Infection and Latency.Current topics in microbiology and immunology · 2025Article
- Article
- Mechanism of DNA capture by the MukBEF SMC complex and its inhibition by a viral DNA mimic.Cell · 2025Article
- 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 · 2025Article
- RAB3GAP2 dysregulation in adult T-cell leukemia/lymphoma (ATLL) compared to acute lymphoblastic leukemia (ALL): a molecular perspective.BMC research notes · 2025Article
- Loop-extrusion-mediated plasmid DNA cleavage by the bacterial SMC Wadjet complex.Molecular cell · 2025Article
- Regulation of viral replication by host restriction factors.Frontiers in immunology · 2025Review
- HIV capsids: orchestrators of innate immune evasion, pathogenesis and pandemicity.The Journal of general virology · 2025Review
- SMC5/6-Mediated Transcriptional Regulation of Hepatitis B Virus and Its Therapeutic Potential.Viruses · 2024Review
- Human Smc5/6 recognises transcription-generated positive DNA supercoils.Nature communications · 2024Article
- Positive Selection Drives the Evolution of the Structural Maintenance of Chromosomes (SMC) Complexes.Genes · 2024Article
- CRL4-DCAF1 Ubiquitin Ligase Dependent Functions of HIV Viral Protein R and Viral Protein X.Viruses · 2024Review
- Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors.
Funding
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.
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