BET inhibitors suppress lytic DNA replication [Akata-Zta RNA-seq]

Lytic infection by the Epstein-Barr virus (EBV) poses numerous health risks, such as infectious mononucleosis and lymphoproliferative disorder. We demonstrate that JQ1 and other BET inhibitors block two different steps in the sequential cascade of the EBV life cycle: expression of the immediate-early gene BZLF1 and lytic genome replication. This represents a novel mode of action for antiviral drugs that may increase efficacy and decrease emergence of resistance. The RNA-seq data below show that the second block causes a decrease in expression of late but not early lytic genes. Overall design: (A) RNA-seq from Akata-Zta pretreated with JQ1 or vehicle, then treated with doxycycline or vehicle, experiment performed in triplicate. (B) RNA-seq from Akata-Zta pretreated with I-BET, then treated with doxycycline or vehicle, experiment performed in triplicate.