BET inhibitors suppress lytic DNA replication [Akata-Zta DNA-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 sequenced total DNA data below show that JQ1 and I-BET cause a decrease in EBV genome replication after induction. (A) Total DNA from Akata-Zta pretreated with JQ1 or vehicle, treated with doxycycline or vehicle, experiment performed in triplicate. (B) As in (A) but pretreated with I-BET or RVX-208.