ArticleNature microbiology2022
Epigenetic silencing by the SMC5/6 complex mediates HIV-1 latency.
Article in Nature microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- The Multifunctional SMC5/6 Complex in Genome Stability, Antiviral Restriction, and Human Disease.Current issues in molecular biology · 2026Review
- Epigenetic mechanisms of retroviral regulation: a comparative review.Epigenetics & chromatin · 2026Review
- Longitudinal plasma proteomic signatures of elite and viremic spontaneous HIV controllers.Nature communications · 2026Article
- Production and Purification of the Human SMC5/6 Core Complex from S. cerevisiae.Methods in molecular biology (Clifton, N.J.) · 2026Article
- SMC5/6-mediated plasmid silencing is directed by SIMC1-SLF2 and antagonized by the SV40 large T antigen.eLife · 2025Article
- Evolutionary interplay between viruses and R-loops.FEBS letters · 2025Review
- Small molecule inhibition of SUMOylation increases expression from AAV vectors both during and after initial transduction in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Immune regulation by the SUMO family.Nature reviews. Immunology · 2025Review
- Chromatin Control of EBV Infection and Latency.Current topics in microbiology and immunology · 2025Article
- Comprehensive SUMO Proteomic Analyses Identify HIV Latency-Associated Proteins in Microglia.Cells · 2025Article
- The emerging roles of ubiquitin-like modifications in regulating HIV replication and host defense.Frontiers in cellular and infection microbiology · 2025Review
- 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
- ORC1 enhances repressive epigenetic modifications on HIV-1 LTR to promote HIV-1 latency.Journal of virology · 2024Article
- The histone methyltransferase SETD2 regulates HIV expression and latency.PLoS pathogens · 2024Article
- The cell biology of HIV-1 latency and rebound.Retrovirology · 2024Review
- The SMC5/6 complex: folding chromosomes back into shape when genomes take a break.Nucleic acids research · 2024Review
- PTEN Mediates the Silencing of Unintegrated HIV-1 DNA.Viruses · 2024Article
- Genome control by SMC complexes.Nature reviews. Molecular cell biology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
After viral entry and reverse transcription, HIV-1 proviruses that fail to integrate are epigenetically silenced, but the underlying mechanism has remained unclear. Using a genome-wide CRISPR/Cas9 knockout screen, we identified the host SMC5/6 complex as essential for this epigenetic silencing. We show that SMC5/6 binds to and then SUMOylates unintegrated chromatinized HIV-1 DNA. Inhibition of SUMOylation, either by point mutagenesis of the SMC5/6 component NSMCE2-a SUMO E3 ligase-or using the SUMOylation inhibitor TAK-981, prevents epigenetic silencing, enables transcription from unintegrated HIV-1 DNA and rescues the replication of integrase-deficient HIV-1. Finally, we show that blocking SMC5/6 complex expression, or inhibiting its SUMOylation activity, suppresses the establishment of latent HIV-1 infections in both CD4+ T cell lines and primary human T cells. Collectively, our data show that the SMC5/6 complex plays a direct role in mediating the establishment of HIV-1 latency by epigenetically silencing integration-competent HIV-1 proviruses before integration.
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Registered trials
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.