Humanized Mouse Core

核心A项目摘要/摘要 这个核心的主要目标是产生人源化的小鼠，可以用来测试HCMV潜伏期和 利用项目1-5中产生的人巨细胞病毒突变体重新激活和造血。的长期目标是 核心A是产生huBLT小鼠，以回答体内关于HCMV潜伏期、重新激活和 基于本计划内嵌的各种研究中提出的体外巨细胞病毒模型的造血 项目。首先，Core将产生huBLT小鼠来分析在项目1-4中产生的HCMV突变 能够建立和维持潜伏期，并在使用G-CSF和AMD-3100治疗后重新激活。一次 项目1-4将确定对人类巨细胞病毒很重要的信号通路和/或分泌因子 潜伏期和重新激活，核心A将使用化学抑制剂，中和抗体， 表达shRNA的重组HCMV和/或重新激活所需的细胞因子/生长因子的添加。 其次，Core将分析感染WT HCMV(项目5)或病毒的huBLT小鼠的造血功能 突变体(项目1-4)，然后将使用化学抑制剂、中和抗体、 表达shRNAs的重组人巨细胞病毒和/或添加造血所需的细胞因子/生长因子。

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.