The carboxy terminus of the herpesvirus saimiri ORF 57 gene contains domains that are required for transactivation and transrepression

Herpesvirus saimiri (HVS) ORF 57 is homologous to genes identified in all c lasses of herpesviruses. We have previously shown that ORF 57 encodes a mul tifunctional protein, responsible for both transactivation and repression o f viral gene expression at a post-transcriptional level. This suggests that the ORF 57 protein shares some functional similarities with the herpes sim plex virus IE63/ICP27 and Epstein-Barr virus Mta proteins. However, little is known about the functional domains responsible for the properties of ORF 57 due to the limited homology shared between these proteins. In this repo rt, we have identified the functional domains responsible for transactivati on and repression by the ORF 57 protein. We demonstrate that the carboxy te rminus is required for ORF 57 transactivation, repression and an intense SC -35 nuclear spotting. This region contains two highly conserved motifs amon gst its homologues, a zinc finger-like motif and a highly hydrophobic domai n. We further show that the hydrophobic domain is required for transactivat ion and is also involved in nuclear localization of the ORF 57 protein, whe reas the zinc finger-like domain is required for transactivation, repressio n and the intense SC-35 nuclear spotting.