{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hopcraft SE"],"funding":["American Cancer Society","NIDCR NIH HHS","NCI NIH HHS","National Institutes of Health","NIGMS NIH HHS"],"pagination":["e1007267"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6136816"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(9)"],"pubmed_abstract":["Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of three human malignancies, the endothelial cell cancer Kaposi's sarcoma, and two B cell cancers, Primary Effusion Lymphoma and multicentric Castleman's disease. KSHV has latent and lytic phases of the viral life cycle, and while both contribute to viral pathogenesis, lytic proteins contribute to KSHV-mediated oncogenesis. Reactivation from latency is driven by the KSHV lytic gene transactivator RTA, and RTA transcription is controlled by epigenetic modifications. To identify host chromatin-modifying proteins that are involved in the latent to lytic transition, we screened a panel of inhibitors that target epigenetic regulatory proteins for their ability to stimulate KSHV reactivation. We found several novel regulators of viral reactivation: an inhibitor of Bmi1, PTC-209, two additional histone deacetylase inhibitors, Romidepsin and Panobinostat, and the bromodomain inhibitor (+)-JQ1. All of these compounds stimulate lytic gene expression, viral genome replication, and release of infectious virions. Treatment with Romidepsin, Panobinostat, and PTC-209 induces histone modifications at the RTA promoter, and results in nucleosome depletion at this locus. Finally, silencing Bmi1 induces KSHV reactivation, indicating that Bmi1, a member of the Polycomb repressive complex 1, is critical for maintaining KSHV latency."],"journal":["PLoS pathogens"],"pubmed_title":["Chromatin remodeling controls Kaposi's sarcoma-associated herpesvirus reactivation from latency."],"pmcid":["PMC6136816"],"funding_grant_id":["CA019014","CA228172","R01 CA163217","131996-PF-18-046-01-MPC","R01 CA228172","CA096500","T32 CA009156","R01 GM100919","P01 CA019014","DE023946","R01 DE018304","CA163217","R01 DE023946","R01 CA096500"],"pubmed_authors":["Hopcraft SE","Dittmer DP","Frye S","Damania B","Pattenden SG","James LI"],"additional_accession":[]},"is_claimable":false,"name":"Chromatin remodeling controls Kaposi's sarcoma-associated herpesvirus reactivation from latency.","description":"Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of three human malignancies, the endothelial cell cancer Kaposi's sarcoma, and two B cell cancers, Primary Effusion Lymphoma and multicentric Castleman's disease. KSHV has latent and lytic phases of the viral life cycle, and while both contribute to viral pathogenesis, lytic proteins contribute to KSHV-mediated oncogenesis. Reactivation from latency is driven by the KSHV lytic gene transactivator RTA, and RTA transcription is controlled by epigenetic modifications. To identify host chromatin-modifying proteins that are involved in the latent to lytic transition, we screened a panel of inhibitors that target epigenetic regulatory proteins for their ability to stimulate KSHV reactivation. We found several novel regulators of viral reactivation: an inhibitor of Bmi1, PTC-209, two additional histone deacetylase inhibitors, Romidepsin and Panobinostat, and the bromodomain inhibitor (+)-JQ1. All of these compounds stimulate lytic gene expression, viral genome replication, and release of infectious virions. Treatment with Romidepsin, Panobinostat, and PTC-209 induces histone modifications at the RTA promoter, and results in nucleosome depletion at this locus. Finally, silencing Bmi1 induces KSHV reactivation, indicating that Bmi1, a member of the Polycomb repressive complex 1, is critical for maintaining KSHV latency.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Sep","modification":"2026-06-13T04:02:27.448Z","creation":"2019-03-26T23:57:13Z"},"accession":"S-EPMC6136816","cross_references":{"pubmed":["30212584"],"doi":["10.1371/journal.ppat.1007267"]}}