THE INTRANUCLEAR LOCATION OF A HERPES-SIMPLEX VIRUS DNA-BINDING PROTEIN IS DETERMINED BY THE STATUS OF VIRAL-DNA REPLICATION

The herpes simplex viral DNA-binding protein, ICP8, is targeted to 2 different locations in the cell nucleus as part of its maturation pathway. Prior to viral DNA synthesis ICP8 was found at discrete prereplicative sites throughout the nucleus, where it exhibited a high-salt labile association wiht the nuclear matrix. During viral DNA replication ICP8 was localized in randomly distributed replication compartments, where it is bound to viral DNA. Initation of viral DNA replication caused the protein to move from the prereplicative sites to the replication compartments, while inhibition of replication caused movement in the opposite direction. In cells where viral DNA synthesis was proceeding, a minor population of ICP8 may also have been associated with the prereplicative sites. The prereplicative sites may serve as a nulcear reservoir for ICP8 not bound to replicating or progeny DNA. [African green monkey kidney Vero and rabbit skin cells were used in these studies.].