Fig. 1.

Schematic representation of early events in HSV-1-infected cells. (A) Cell infected with a ΔICP mutant at low pfu per cell. The schematic diagram illustrates that VP16 enters the nucleus concomitantly with the release of viral DNA from capsids at the nuclear pore. VP16 associates with cellular proteins Oct1 and HCF and transactivates α gene promoters. α proteins are made, but the expression of β and γ genes does not ensue. (B) Cell infected with wild-type virus. As reported earlier, ICP0 interacts with CoREST and displaces HDAC1 from the CoREST–REST complex. HDAC1 and CoREST are phosphorylated and translocated to the cytoplasm. β and γ genes are expressed. (C) Predicted role of a dominant-negative CoREST that dissociates HDAC1 from the CoREST–REST complex. If ICP0 enables the transition from α to β and γ gene expression by dissociating HDAC1/2 from the CoREST–REST complex, then a dominant-negative CoREST that displaces HDAC1 from the complex would substitute for ICP0 to enable enhanced replication of ΔICP0 mutant virus.