VIRAL AND CELLULAR GENE EXPRESSION DURING CMV INFECTION

巨细胞病毒感染时病毒和细胞基因的表达。 CMV感染和208个非冗余病毒基因的表达改变 宿主细胞在许多方面可能是重要的病毒生存在 免疫活性宿主以及用于产生急性和慢性 免疫受损宿主的疾病。 最近一代的 含有数千个人类cDNA的微阵列， 全面同时采样病毒表达， 感染过程中的细胞基因表达。 A的初步筛选 10，000人类基因微阵列显示，到24 hpi，CMV 显著激活了编码特定 基因的种类（细胞DNA复制、蛋白酶体成分、RNA 剪接等），但明显抑制转录水平 从参与细胞运动、炎症、血管 调节和免疫反应的方式，模仿的影响， 皮质类固醇对这些细胞的作用 我们建议将所有CMV 沿着10，000个细胞基因，以：（i）鉴定病毒基因 控制免疫相关宿主细胞基因表达的抑制， 和（ii）研究表达主要的病毒基因的作用， 调节蛋白IE1，IE2和UL37在激活和抑制 病毒和细胞基因表达。病毒微阵列评价 在基因互补和确定的突变体方面不同的菌株 将被用来系统地绘制那些控制 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起作用。 这些 分析将导致对病毒和细胞遗传的理解， 伴随调节功能的途径将侧重于了解 这些功能在激活或抑制细胞内 基因表达和阻断细胞凋亡。这些研究将揭示 病毒调节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 保持有利的条件，我们相信 CMV改变宿主细胞并成功复制，逃避自然和 适应性免疫监视，并导致免疫功能低下的疾病 个体

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.