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)广泛存在于成人中，以潜伏状态存在于B淋巴细胞内，终生存在。感染。单核细胞增多症是一种公认的、与EBV相关的自限性急性感染。然而，越来越多的疾病被认为与这种特殊的疱疹病毒有关，如噬血细胞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、霍奇金氏病和胃癌。通过对这些疾病的研究表明，活体感染的细胞靶点和病毒潜伏的方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的细胞中都有大量表达，无论潜伏期是什么，因此其表达经常被用作EBV与某些疾病关联的敏感指标。在本研究中，临床相关性…EBER1表达的原位杂交流式分析(ISH/FCM)更多地用于定量鉴定EBV感染的细胞。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EBER1mRNA荧光标记探针的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，前者就不那么敏感了。EBER1在不同细胞系中的表达水平不同，且单个细胞群体内的荧光强度分布较广，表明EBER1的表达受多种机制控制。重要的是，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，但正常对照组或急性传染性单核细胞增多症患者却检测不到。EBER1ISH/FCM可以作为一种有用的工具，相对容易地顺序监测这些患者的靶细胞和感染模式。通过应用EBER1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，将获得进一步的信息。较少

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