VIRAL AND CELLULAR GENE EXPRESSION DURING CMV INFECTION

巨细胞病毒感染过程中病毒和细胞基因的表达 巨细胞病毒感染与208个非冗余病毒基因表达改变 宿主细胞在许多方面可能对病毒在 免疫能力强的宿主以及急性和慢性的产生 免疫受损宿主中的疾病。最新一代的 含有数千个人类cDNA的微阵列使我们有可能 全面同步的病毒和病毒样本表达 感染过程中细胞基因的表达。金黄色葡萄球菌的初步筛选 10000个人类基因芯片显示，由24HPI、CMV 显著激活编码特定基因的转录本水平 基因类别(细胞DNA复制、蛋白酶体成分、RNA 剪接等)，但显著抑制转录水平 来自与细胞运动、炎症、血管相关的基因类别 以模拟影响的方式进行调节和免疫反应 这些细胞上的皮质类固醇。我们建议将所有CMV 基因和10,000个细胞基因：(I)识别病毒基因 控制免疫相关宿主细胞基因表达的抑制， 以及(Ii)研究表达主要病毒基因的作用 调控蛋白IE1、IE2和UL37在细胞周期调控中的作用 病毒和细胞基因的表达。病毒的基因芯片评价 基因补充性不同的菌株和已定义的突变体 将被用来系统地绘制控制这些病毒的功能 抑制细胞基因表达，并了解如何 其他病毒基因的表达可能在这一过程中发挥作用。这些 分析将导致对病毒和细胞遗传的理解 伴随调节器功能的途径将侧重于理解 这些功能在激活或抑制细胞方面所起的作用 基因表达和阻断细胞凋亡。这些研究将揭示 病毒调控基因在控制基因表达中的作用 不同的细胞类型。正是这种在多个层面上互动的能力 并保持我们认为领先的有利条件 CMV改变宿主细胞并成功复制，避开自然和 适应性免疫监测，并导致免疫受损的疾病 个人。

Viral and Cellular Gene Expression During Cytomegalovirus Infection. Infection with CMV and expression of 208 nonredundant viral genes alters host cells in many ways that may be important for virus survival in the immunocompetent host as well as for the generation of acute and chronic diseases in the immunocompromised host. The recent generation of microarrays with thousands of human cDNAs makes it possible to comprehensively and simultaneously sample expression of viral and cellular gene expression during infection. Preliminary screening of a 10,000 human gene microarray has shown that, by 24 hpi, CMV significantly activates levels of transcripts encoding particular classes of genes (cellular DNA replication, proteasome components, RNA splicing, and others), but markedly suppresses levels of transcripts from gene classes involved in cell motility, inflammation, vascular regulation and immune response in a manner that mimics the impact of corticosteroids on these same cells. We propose to include all CMV genes along with 10,000 cellular genes to: (i) identify the viral genes controlling the suppression of immune-related host cell gene expression, and (ii) investigate the role of the viral genes expressing the major regulatory proteins IE1, IE2 and UL37 in activation and suppression of viral and cellular gene expression. Microarray evaluation of viral strains that differ in their complement of genes and of defined mutants will be used to systematically map those viral functions that control suppression of cellular gene expression and to understand how the expression of other viral genes may play a role in this process. These analyses will lead to an understanding of viral and cellular genetic pathways that accompany regulator functions will focus on understanding the role that these functions play in activating or repressing cellular gene expression and blocking apoptosis. These studies will reveal the role viral regulatory genes have in controlling gene expression in different cell types. It is this ability to interact on many levels with the host and maintain favorable conditions that we believe leads CMV to alter the host cell and replicate successfully, evade natural and adaptive immune surveillance, and cause disease in immunocompromised individuals.