Establishment of herpesvirus latency. A. Herpes Simplex Virus Type 1 (HSV-1). Infection of a sensory neuron allows for nuclear entry of viral DNA but not the tegument transactivator VP16. Viral immediate early (IE) genes are silenced. B. Human Cytomegalovirus (HCMV). Infection of a CD34+ hematopoietic progenitor cell allows for nuclear entry of viral DNA but not the tegument transactivator pp71. Viral IE genes are silenced by Daxx and an unidentified (?) trans-dominant, HDAC-independent mechanism. C. Epstein-Barr Virus (EBV). Infection of a memory B cell allows for nuclear entry of viral DNA. Tegument transactivators for EBV are uncharacterized. At least one IE gene (Z) and two early genes (BALF1 and BHRF1) are expressed. Z promotes B cell proliferation and BALF1/BHRF1 inhibit apoptosis, both of which appear to be required for the efficient establishment of latency. Z is unable to fully activate lytic phase gene expression because the viral genome is unmethylated.