Dr. Maul and his colleagues have identified sites in the nucleus of uninfected cells which are utilized by three different DNA viruses for depositing viral DNA and initiating transcription and replication. These domains, ND10, contain several interferon-upregulated proteins. Herpesvirus, adenovirus and SV40 are able to specifically deposit their genomes at ND10 after nuclear entry and before transcription begins. This deposition is virus DNA-dependent and has lead to the hypothesis that a DNA transport mechanism exists. The applicant proposes to study this phenomenon by determining the targeting signals in DNA from several virus families. This will be accomplished by identifying the location of expression vectors relative to specific nuclear domains. These vectors will contain overlapping viral genome fragments. Second, they will define the host cell proteins that bind to the identified viral target sequences. Third, they will determine the functional significance of virus genome deposition at the specific nuclear domain by quantitative assays that determine the transcriptional capacity of specifically targeted and untargeted genes.
