Model illustrating how S-like-phase CDKs temporally control late gene transcription during the EBV lytic phase. BDLF4 (encoded by an EBV E gene) (17, 25) is expressed during early lytic replication, at which time L gene expression is suppressed, because the unphosphorylated form of BDLF4 is rapidly degraded. As the lytic cycle progresses, the activities of cyclin E- and cyclin A-associated CDK proteins (S-phase CDKs) increase (19). Activated S-phase CDKs phosphorylate BDLF4, stabilizing the protein. Phosphorylated BDLF4 engages in vPIC formation with five other viral proteins and transactivates L gene expression in the middle-to-late phase of lytic replication. P, phosphorylation; RNAP II, RNA polymerase II complex.