Role of ND10 and Recombination in HSV-1 DNA Replication

描述（由申请人提供）：人类单纯疱疹病毒1型（HSV-1） DNA复制与称为ND10的核基质结合结构域密切相关。一些参与细胞重组和修复的蛋白质已被证明定位于ND10，一些蛋白质如RPA和RAD51已被证明被招募到病毒复制区室。该项目的主要重点是验证细胞重组蛋白，特别是在ND10发现的细胞重组蛋白与HSV-1复制蛋白和病毒复制区室的亚组装相关的假设。这些蛋白的细胞分布将通过感染或转染细胞的免疫细胞化学染色来表征。这些细胞复制蛋白在病毒生命周期中的作用将使用DNA复制和修复缺陷的细胞系进一步表征。对病毒复制蛋白与nd10相关重组蛋白的分析将进一步了解宿主细胞相互作用，这对病毒感染很重要。这可能反过来导致发现针对这种非常成功的人类病原体的抗病毒药物。

DESCRIPTION (provided by applicant): Human Herpes Simplex Virus Type-1 (HSV-1) DNA replication is closely associated with nuclear matrix-bound domains called ND10. Several proteins involved in cellular recombination and repair have been shown to localize to ND10 and some proteins such as RPA and RAD51 have been shown to be recruited to viral replication compartments. The main focus of this project is to test the hypothesis that cellular recombination proteins, particularly those found at ND10, are associated with subassemblies of HSV-1 replication proteins and viral replication compartments. The cellular distribution of these proteins will be characterized via immunocytochemical staining of infected or transfected cells. The roles of these cellular replication proteins in the viral life cycle will be further characterized using cell lines defective in DNA replication and repair. Analysis of viral replication proteins with respect to ND10-associated recombination proteins will provide further understanding of host cell interactions that are important for viral infection. This may in turn lead to the discovery of antiviral agents against this highly successful human pathogen.