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

爱泼斯坦-巴尔病毒（EBV）在成年人群中流行，并以潜伏形式在B淋巴细胞中终生存在。感染。单核细胞增多症是一种公认的，自限性EBV相关的急性感染。然而，现在已知越来越多的疾病与这种特殊的疱疹病毒有关，如噬血细胞性淋巴组织细胞病（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。通过对这些疾病的研究表明，重要感染的细胞靶点和病毒潜伏的模式在很大程度上改变了ebv相关疾病的发病机制。EBV编码的小RNA-1 （EBER1）在几乎所有感染EBV的细胞中都大量表达，无论其潜伏期如何，因此其表达通常被用作EBV与某些疾病关联的敏感指标。本研究对EBER1表达的原位杂交流式细胞分析法（ISH/FCM）进行了评价，以定量鉴定ebv感染细胞。初步实验表明，与使用碱性磷酸酶标记探针的标准ISH相比，使用荧光标记的EBER1 mRNA探针的ISH/FCM能够更定量地评估样本群体中感染细胞的比例。然而，当感染细胞的比例小于1%时，前者的敏感性较低。EBER1的表达水平在不同细胞系间存在差异，且荧光强度在单个细胞群内分布较广，说明EBER1的表达受多种机制控制。重要的是，病毒感染的细胞在HLH和CAEBV患者的外周血淋巴细胞中很容易检测到，但在正常对照或急性感染性单核细胞增多症患者中却检测不到。EBER1 ISH/FCM可以作为一种有用的工具，相对容易地依次监测这些患者的靶细胞和感染模式。通过对EBER1表达的多参数分析，结合不同ebv相关基因表达和表面抗原分析，可以获得进一步的信息。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