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.
|Wilkinson, Dianna E; Weller, Sandra K (2006) Herpes simplex virus type I disrupts the ATR-dependent DNA-damage response during lytic infection. J Cell Sci 119:2695-703|
|Wilkinson, Dianna E; Weller, Sandra K (2005) Inhibition of the herpes simplex virus type 1 DNA polymerase induces hyperphosphorylation of replication protein A and its accumulation at S-phase-specific sites of DNA damage during infection. J Virol 79:7162-71|
|Wilkinson, Dianna E; Weller, Sandra K (2004) Recruitment of cellular recombination and repair proteins to sites of herpes simplex virus type 1 DNA replication is dependent on the composition of viral proteins within prereplicative sites and correlates with the induction of the DNA damage response. J Virol 78:4783-96|