PARP1 restricts Epstein Barr Virus lytic reactivation by binding the BZLF1 promoter

- CTCF binding to the EBV genome is not functionally relevant to viral reactivation.
- PARP1 colocalizes with CTCF at the EBV BZLF1 CTCF binding site.
- EBV reactivation attenuates PARP activity through Zta.
- PARP1 knockdown increases Zta binding to the BZLF1 promoter.
- PARP1 binds to the EBV BZLF1 lytic switch promoter to restrict lytic reactivation.

The Epstein Barr virus (EBV) genome persists in infected host cells as a chromatinized episome and is subject to chromatin-mediated regulation. Binding of the host insulator protein CTCF to the EBV genome has an established role in maintaining viral latency type, and in other herpesviruses, loss of CTCF binding at specific regions correlates with viral reactivation. Here, we demonstrate that binding of PARP1, an important cofactor of CTCF, at the BZLF1 lytic switch promoter restricts EBV reactivation. Knockdown of PARP1 in the Akata-EBV cell line significantly increases viral copy number and lytic protein expression. Interestingly, CTCF knockdown has no effect on viral reactivation, and CTCF binding across the EBV genome is largely unchanged following reactivation. Moreover, EBV reactivation attenuates PARP activity, and Zta expression alone is sufficient to decrease PARP activity. Here we demonstrate a restrictive function of PARP1 in EBV lytic reactivation.