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

EB病毒（Epstein-Barr virus，EBV）是一种在成年人中普遍存在的病毒，它以潜伏形式存在于B淋巴细胞中，并伴随终生。感染单核细胞增多症是一种公认的自限性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，例如噬血细胞性淋巴组织细胞增多症（HLH）、慢性活动性EBV感染（CAEBV）和各种恶性肿瘤，包括鼻咽癌、霍奇金病和胃癌。通过研究这些疾病已经表明，活体感染的细胞靶点和病毒的潜伏模式极大地改变了EBV相关疾病的发病机制。EB病毒编码的小RNA-1（EBER 1）在几乎所有感染EB病毒的细胞中大量表达，无论潜伏模式如何，因此其表达通常用作EB病毒与某些疾病相关的敏感指标。在这项研究中， 关于我们 应用原位杂交/流式细胞术（ISH/FCM）检测EBER 1的表达，以定量鉴定EBV感染细胞。初步的实验表明，ISH/FCM使用荧光标记的探针EBER 1 mRNA使更多的定量评价的样本群体内的感染细胞的分数比标准ISH使用碱性磷酸酶标记的探针。但当感染细胞的比例小于1%时，前者的敏感性较低。EBER 1的表达水平在不同的细胞系中是不同的，并且荧光强度在单个细胞群体中的分布相对较宽，表明EBER 1的表达受多种机制控制。重要的是，在HLH和CAEBV患者的外周血淋巴细胞中很容易检测到病毒感染的细胞，但在正常对照组或急性传染性单核细胞增多症患者中却不能检测到。EBER 1 ISH/FCM可作为一种有用的工具，以监测这些患者的靶细胞和感染模式相对容易。进一步的信息将通过应用EBER 1表达的多参数分析结合不同的EBV相关基因表达和表面抗原分析来获得。少

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