Regulation of replication and latency EBV EBNAs

EB病毒（EBV）是一种γ疱疹病毒，可引起传染性单核细胞增多症， 各种人类淋巴癌和上皮癌。免疫功能低下是EBV的危险因素 与恶性肿瘤相关的疾病，如移植后淋巴增生性疾病， 移植患者和中枢神经系统淋巴瘤以及全身性淋巴瘤的比例 EB病毒与艾滋病相关。EB病毒也与伯基特淋巴瘤、鼻咽淋巴瘤、淋巴结转移有关。 癌、鼻T细胞淋巴瘤和霍奇金淋巴瘤和胃癌的子集。后 原发性感染的个体将保持潜伏感染EBV，这是一个终身的水库， 感染的细胞，这是在随后的恶性疾病的发展因素。 EBV感染培养物中的B细胞导致永生化B细胞系的生长，并且EBNA 2是其中一种。 EBV编码的蛋白质对这一过程至关重要。EBNA 2通过靶向aDMA改变细胞基因表达 结合蛋白，CBF 1/RBPJk，并将CBF 1抑制的启动子转换为激活状态。在其 靶向CBF 1，EBNA 2模拟活化的Notch信号传导。建议重新评估 通过比较EBNA 2和NotchIC与细胞蛋白的相互作用来鉴定作为Notch模拟物的EBNA 2， EBNA 2和NotchIC共有的蛋白伴侣与EBNA 2和NotchIC特有的蛋白伴侣相比， EBNA 2或NotchIC。高通量筛选技术为蛋白质-蛋白质鉴定提供了新的工具 相互作用，并可以提供深入了解个别蛋白质的功能和相互作用之间的相互作用， 目的蛋白和细胞信号网络。我们的方法将是筛选蛋白质组芯片， 约翰霍普金斯高中生物学中心的房子，有EBNA 2和Notch 11 C和Notch 2 IC。两 最初将使用不同的蛋白质组芯片：一个打印有5000种人类蛋白质，另一个打印有1000种人类蛋白质。 独特的转录因子特异性芯片，包含1003个已知和预测的人类转录因子。 在后续研究中，蛋白质组芯片将作为高通量药物筛选平台， 差异性阻断EBNA 2与NotchIC与细胞蛋白相互作用的化合物， 具有抗EB病毒治疗的潜力。

Epstein-Barr virus (EBV) is a gamma herpesvirus that causes infectious mononucleosis and is associated with a variety of human lymphoid and epithelial cancers. Immunocompromise is a risk factor for EBV associated disease with malignancies such as post-transplant lymphoproliferative disease arising in transplant patients and central nervous system lymphoma and a proportion of systemic lymphomas being EBV associated in AIDS patients. EBV is also associated with Burkitt's lymphoma, nasopharyngeal carcinoma, nasal T cell lymphoma, and a subset of Hodgkin's lymphomas and gastric carcinomas. After primary infection an individual will remain latently infected with EBV and it is this life-long reservoir of latently infected cells that is a factor in the development of subsequent malignant disease. EBV infection of B cells in culture leads to the outgrowth of immortalized B cell lines and EBNA2 is one of the EBV encoded proteins essential for this process. EBNA2 alters cellular gene expression by targeting aDMA binding protein, CBF1/RBPJk, and switching CBF1 repressed promoters to an activated state. In its targeting of CBF1, EBNA2 mimics activated Notch signaling. It is proposed to re-evaluate the model of EBNA2 as a Notch mimic by comparing EBNA2 and NotchIC interactions with cellular proteins to identify protein partners that are shared by both EBNA2 and NotchIC versus protein partners that are unique to EBNA2 or NotchIC. High throughput screening assays provide new tools for identifying protein-protein interactions and can provide insight both into individual protein functions and into interactions between the protein of interest and cell signaling networks. Our approach will be to screen proteomic chips generated in house by the Johns Hopkins High Throughput Biology Center with EBNA2 and NotchllC and Notch2IC. Two different proteomic chips will be utilized initially: One printed with 5000 human proteins and the second a unique transcription factor specific chip containing 1003 known and predicted human transcription factors. In follow-up studies, the proteomic chips will be used as a high throughput drug screening platform to identify compounds that differentially block EBNA2 versus NotchIC interactions with cell proteins and that hence would have anti-EBV therapeutic potential.