The UL133-138 gene locus and its effect on latency and reactivation. (A) UL138 (red) suppresses virus replication for latency and UL135 (green) is required to overcome these suppressive effects for replication and reactivation. UL136 is expressed as at least five protein isoforms. Like UL133 and UL138, UL136p23/p19 are pro-latency proteins, whereas like UL135, UL136p33 and UL136p26 favor virus replication and are required for reactivation. UL136p25 has context-dependent functions, which need to be further defined. (B) Temporal regulation of the UL133-UL138 genes. Important in this cascade is the differential kinetics of gene expression: early expression of UL135 and UL138 and the early-late expression of UL136 isoforms. Maximal UL136 expression depends on viral genome synthesis, indicating that induction of its expression may function to commit the virus to replicative state or that it mediates the transition between UL138-dominant latent and UL135-dominant replicative states. IE is an acronym for immediate early and E/L denotes early/late.