%0 Journal Article
%T Chromatin remodeling controls Kaposi's sarcoma-associated herpesvirus reactivation from latency
%A Blossom Damania
%A Dirk P. Dittmer
%A Lindsey I. James
%A Samantha G. Pattenden
%A Sharon E. Hopcraft
%A Stephen Frye
%J -
%D 2018
%R 10.1371/journal.ppat.1007267
%X 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
%K Histones
%K Kaposi's sarcoma-associated herpesvirus
%K Gene expression
%K Chromatin
%K Nucleosomes
%K Viral replication
%K Epigenetics
%K Vero cells
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007267