Pathogenesis of Diverse Clinical Manifestations of EBV-Related Disorders : Mechanisms of Target-Cell Specific Infection, Regulation of Viral Gene Expression and Clonal Expansion.

EBV 相关疾病的多种临床表现的发病机制：靶细胞特异性感染的机制、病毒基因表达的调节和克隆扩增。

基本信息

批准号：
10670709
负责人：
OHTA Kazuhide
金额：
$ 1.98万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

Epstein-Barr virus (EBV) is prevalent among adult population and it persists within B lymphocytes in latent forms throughout life. Infection. mononucleosis is a well recognized, self-limited EBV- related acute infection. However, increasing numbers of illness are now known to be associated with this particular herpes virus, such as hemophagocytic lymphohistiocytosis (HLH), chronic active EBV infection (CAEBV) and various malignant neoplasms, including nasopharyngeal carcinoma, Hodgikin's disease and gastric cartinoma. It has been suggested by studying these diseases that the cellular targets of vital infection and the modes of the latency of viruses greatly the modify pathogenesis of EBV-related illnesses. EBV-encoded small RNA-1 (EBER1) is expressed in abundance in virtually every cell infected with EBV, regardless of the mode of latency and therefore its expression is often used as a sensitive indicator of EBV association with certain illnesses. In this study, the clinical relevance … More of in situ hybridization flowctyometric analysis (ISH/FCM) of EBER1 expression was evaluated to identify EBV-infected cells quantitatively. Preliminary experiments showed that ISH/FCM using a fluorescence-labeled probe for EBER1 mRNA enabled more quantitative evaluation of the fraction of the infected cells within a sample population than standard ISH using alkaline phosphatase-labeled probe. However, the former was less sensitive when the fraction of the infected cells was smaller than 1 percent. Levels of EBER1 expression were various among different cell lines and the distribution of the fluorescence intensity within a single cell population is relatively wide, indicating that EBER1 expression is controlled by multiple mechanisms. Importantly, the virus-infected cells were easily detectable within peripheral lymphocytes from patients with HLH and CAEBV, but not from normal controls or patients with acute infectious mononucleosis. EBER1 ISH/FCM may serve as a useful tool to monitor sequentially the target cells and the mode of infection in these patients with relative ease. Further information will be available by applying multiparameter analysis of EBER1 expression in combination with different EBV-related gene expression and surface antigen analysis. Less

Epstein-Barr病毒（EBV）在成年人口中普遍存在，它在B淋巴细胞中一直处于潜在形式。感染。单核细胞增多症是一种公认的，自限的EBV相关急性感染。然而，现在已知越来越多的疾病与这种特定的疱疹病毒有关，例如血型淋巴细胞增多（HLH），慢性活性EBV感染（CAEBV）和各种恶性肿瘤，包括鼻咽癌，霍迪吉克蛋白疾病和霍迪奇基氏病和气候瘤。通过研究这些疾病，已经提出了重要感染的细胞靶标和病毒潜伏期的模式很大，可以改变与EBV相关疾病的发病机理。 EBV编码的小RNA-1（EBER1）在几乎每个感染EBV的细胞中都以丰富的形式表达，而不论潜伏期如何，因此其表达通常被用作EBV与某些疾病的敏感指标。在这项研究中，评估了EBER1表达的临床相关性……更多的原位杂交流量表分析（ISH/FCM），以定量地识别EBV感染的细胞。初步实验表明，使用荧光标记的探针进行EBER1 mRNA的ISH/FCM可以比使用Hocaline磷酸酶标签的探针对样品种群中感染细胞的分数进行更定量的评估。但是，当感染细胞的分数小于1％时，前者的敏感性较小。 EBER1表达水平在不同的细胞系之间是不同的，单个细胞群体中荧光强度的分布相对较宽，表明EBER1表达受到多种机制的控制。重要的是，在患有HLH和CAEBV患者的外周淋巴细胞中，很容易检测到病毒感染的细胞，但不能来自正常对照或急性感染单核细胞增多症患者。 EBER1 ISH/FCM可以用作相对轻松地监测目标细胞和感染方式的有用工具。将通过将EBER1表达的多参数分析与不同的EBV相关基因表达和表面抗原分析一起应用。较少的