{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Irwan ID"],"funding":["U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)","NIAID NIH HHS","U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","Duke | Center for AIDS Research, Duke University","Duke | Center for AIDS Research, Duke University (Duke University Center for AIDS Research)"],"pagination":["2101-2113"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9712108"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(12)"],"pubmed_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 l"],"journal":["Nature microbiology"],"pubmed_title":["Epigenetic silencing by the SMC5/6 complex mediates HIV-1 latency."],"pmcid":["PMC9712108"],"funding_grant_id":["R21-AI157616","P30 AI064518","P30-AI064518","R21 AI157616"],"pubmed_authors":["Cullen BR","Irwan ID","Bogerd HP"],"additional_accession":[]},"is_claimable":false,"name":"Epigenetic silencing by the SMC5/6 complex mediates HIV-1 latency.","description":"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 l","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2026-05-28T21:29:09.263Z","creation":"2025-04-19T22:50:15.94Z"},"accession":"S-EPMC9712108","cross_references":{"pubmed":["36376394"],"doi":["10.1038/s41564-022-01264-z"]}}