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.
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|Negorev, Dmitri G; Vladimirova, Olga V; Kossenkov, Andrew V et al. (2010) Sp100 as a potent tumor suppressor: accelerated senescence and rapid malignant transformation of human fibroblasts through modulation of an embryonic stem cell program. Cancer Res 70:9991-10001|
|Negorev, Dmitri G; Vladimirova, Olga V; Maul, Gerd G (2009) Differential functions of interferon-upregulated Sp100 isoforms: herpes simplex virus type 1 promoter-based immediate-early gene suppression and PML protection from ICP0-mediated degradation. J Virol 83:5168-80|
|Hanson, Laura K; Slater, Jacquelyn S; Cavanaugh, Victoria J et al. (2009) Murine cytomegalovirus capsid assembly is dependent on US22 family gene M140 in infected macrophages. J Virol 83:7449-56|
|Wang, Yan; Tang, Qiyi; Maul, Gerd G et al. (2006) Kaposi's sarcoma-associated herpesvirus ori-Lyt-dependent DNA replication: dual role of replication and transcription activator. J Virol 80:12171-86|
|Davido, David J; Von Zagorski, William F; Maul, Gerd G et al. (2003) The differential requirement for cyclin-dependent kinase activities distinguishes two functions of herpes simplex virus type 1 ICP0. J Virol 77:12603-16|