Figure 2.

Combination of currently available lytic inducers. (A) Combination of iron chelators and HDAC inhibitors. Iron chelators and HDAC inhibitors reactivate EBV lytic cycle through autophagy-dependent and independent pathways, respectively. Their combination could potentially be synergistic in reactivating EBV lytic cycle. (B) Combination of iron chelators and lenalidomide. Combination of lytic inducers with different mechanisms for EBV lytic reactivation may have synergistic effects in reactivating the EBV lytic cycle. Lenalidomide reactivates EBV lytic cycle by suppressing Ikaros, which inhibits the expression of transcription factors that inhibit EBV lytic cycle. Manipulation of Zta expression by iron chelators, together with the suppression of inhibitory factors that prevent Zta transactivation of other lytic genes by lenalidomide, may provide a feed-forward loop for lytic reactivation, thus enhancing EBV lytic induction.