IDENTIFICATION AND CHARACTERIZATION OF HUMAN CYTOMEGALOVIRUS/CELLULAR PROTEINS

人巨细胞病毒(HCMV)是一种广泛存在的机会性病原体，能够建立一种 持续性或潜伏性感染。在大多数情况下，健康人巨细胞病毒感染是良性或无症状的。 个人赛。然而，婴儿和免疫功能低下的成年人一旦感染就会患上严重的疾病。这个 基因组以ET时间有序的方式表达，并分三个独立的阶段出现：即刻早期 即)、早、晚。早期阶段开始于DNA复制之前，进一步分为三个阶段 根据感染过程中早期转录本的表达水平进行亚类划分。/ 几种巨细胞病毒早期启动子的研究已经被用来确定巨细胞病毒早期基因是如何 表达是受调控的。已经鉴定了几个特定的DNA序列和蛋白质。一些人 人巨细胞病毒早期启动子序列与巨细胞病毒特异性蛋白(IE86)结合 环AMP反应元件结合蛋白(CREB)或激活的转录因子等蛋白质 [ATF]。早期启动子的激活需要IE86和IE72蛋白的存在或IE86单独存在。 * UL98早期基因编码58-65 kDa的蛋白质，是嵌套的3‘端开放阅读框家族的一部分，该家族 共享一个多聚腺苷酸化位点。碱性核酸外切酶在新合成的过程中起着至关重要的作用 基因组在成熟过程中的复制副本。我们已经确定HCMV UL98启动子利用 Cre和Gamma(G)能以最佳方式调节这一早期基因的表达。在缺失分析中，T细胞 此外，还涉及类因子元件(Tcp)。研究还表明，CREB蛋白 在凝胶迁移率改变分析中与Cre序列相互作用。然而，与之相关的特定蛋白质 在通过TCF-1和Gire进行调控的情况下，还没有确定位点的特征。我们在以下方面的目标 研究将确定与TCF1元件和GIRE结合的病毒/细胞蛋白(S)。分析了几个问题 这一关键的病毒早期基因的调控机制将提供对早期病毒的整体调控的洞察 基因表达与新型抗病毒治疗的未来发展。

Human cytomegalovirus (HCMV) is a widespread opportunistic pathogen capable of establishing either a persistent or latent infection. In most cases, HCMV infection is benign or asymptomatic in healthy ndividuals. However, serious illness occurs upon infection in infants and immunocompromised adults. The genome is expressed in et temporally ordered manner and occurs in three separate phases: immediate early IE), early, and late. The early phase, which begins just prior to DNA replication, is further divided into three subclasses based on the expression level of early transcripts through the course of infection. / Studies on several HCMV early promoters have been undertaken to determine how HCMV early gene expression is regulated. Several specific DNA sequences as well as proteins have been identified. Some HCMV early promoter sequences are bound by HCMV specific proteins (IE86) as well as such as cellular proteins such as the cyclic AMP response element binding protein (CREB) or activated transcription factor [ATF). Activation of the early promoters requires the presence of IE86 and IE72 proteins or IE86 alone. * The UL98 early gene encodes a 58-65 kDa protein and is part of a family of nested 3' coterminal ORFs that share a polyadenylation site. The alkaline exonuclease plays a critical role in processing newly synthesized replicated copies of genome during maturation. We have determined that the HCMV UL98 promoter utilizes CRE and gamma (g) IRE to optimally regulate the expression of this early gene. In deletion analysis, a Tcell factor-like element (TCP) has also been implicated. Studies have also shown that the protein CREB interacts with the CRE sequences in gel mobility shift assays. However, the specific proteins associated with regulation through the TCF-1 and gIRE sites have yet to be characterized. Our objective in the following studies will be to identify the viral/cellular protein(s) that bind the TCF-1 element and gIRE. The analysis of regulatory mechanisms for this key viral early gene will provide insight into the overall regulation of early gene expression and the future development of novel antiviral therapies.