REPLACEMENT OF THE HERPES-SIMPLEX VIRUS TYPE-1 VMW175 DNA-BINDING DOMAIN WITH ITS VARICELLA-ZOSTER VIRUS COUNTERPART RESULTS IN A PROTEIN WITH NOVEL REGULATORY PROPERTIES THAT CAN SUPPORT VIRUS GROWTH

The alphaherpesviruses encode major immediate early transactivator pro teins that are essential for the expression of later classes of viral genes. We have previously shown that the extensive sequence similarity between the herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV) members of the family (proteins Vmw175 and VZV140k) extend s to function, since a virus which expresses VZV140k in place of Vmw17 5 is able to grow, albeit at reduced efficiency. We have also shown th at the DNA binding characteristics of the isolated DNA binding domains of Vmw175 and VZV140k are related but distinct. In order to assess wh ether the different DNA binding properties of the two protei ns are re sponsible for the differences in their individual transcriptional regu latory functions, we constructed a plasmid and an HSV-1 virus in which the VZV140k DNA binding domain coding sequences replace those of Vmw1 75. The characteristics of the resultant hybrid protein in transfectio n assays and during virus infection suggest that the nature of the DNA binding domain plays a significant role in the transactivation and re pression properties of the Vmw175 family of proteins.