TY - DATA T1 - Chromatin remodeling controls Kaposi's sarcoma-associated herpesvirus reactivation from latency PY - 2018/09/13 AU - Sharon E. Hopcraft AU - Samantha G. Pattenden AU - Lindsey I. James AU - Stephen Frye AU - Dirk P. Dittmer AU - Blossom Damania UR - https://plos.figshare.com/articles/dataset/Chromatin_remodeling_controls_Kaposi_s_sarcoma-associated_herpesvirus_reactivation_from_latency/7086536 DO - 10.1371/journal.ppat.1007267 L4 - https://ndownloader.figshare.com/files/13029833 L4 - https://ndownloader.figshare.com/files/13029836 KW - Kaposi KW - JQ KW - histone deacetylase inhibitors KW - sarcoma-associated herpesvirus reactivation KW - lytic gene expression KW - B cell cancers KW - PTC KW - KSHV lytic gene transactivator RTA KW - Primary Effusion Lymphoma KW - Bmi KW - KSHV reactivation KW - host chromatin-modifying proteins N2 - 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. ER -