Humanized Mouse Core

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CORE A PROJECT SUMMARY/ABSTRACT The primary goal of this Core is to generate humanized mice that can be used to test HCMV latency and reactivation as well as hematopoiesis using HCMV mutants generated in Projects 1-5. The long-term goal of Core A is to generate huBLT mice to answer in vivo questions of HCMV latency, reactivation and hematopoiesis based on in vitro CMV models proposed in the various studies embedded in the Program Project. First, the Core will generate huBLT mice to analyze HCMV mutants generated in Projects 1-4 for their ability to establish and maintain latency and reactivate following treatment with G-CSF and AMD-3100. Once Projects 1-4 will have identified signaling pathways and/or secreted factors that are important for HCMV latency and reactivation, Core A will validate them using chemical inhibitors, neutralizing antibodies, recombinant HCMV expressing shRNAs and/or addition of cytokines/growth factors required for reactivation. Second, the Core will analyze hematopoiesis in huBLT mice infected with WT HCMV (Project 5) or viral mutants (Projects 1-4) and then will validate the results using chemical inhibitors, neutralizing antibodies, recombinant HCMV expressing shRNAs and/or addition of cytokines/growth factors required for hematopoiesis.