REGULATION OF THE EBV LYTIC SWITCH GENE BZLF1

EBV 裂解开关基因 BZLF1 的调控

• 批准号: 2517116
• 负责人: KAREN E WECK
• 金额: $ 9.04万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2517116
• 关键词: B lymphocyte; DNA binding protein; Epstein Barr virus; cell line; gel mobility shift assay; gene expression; gene induction /repression; gene mutation; gene targeting; genetic promoter element; genetic regulation; genome; human tissue; in situ hybridization; latent virus infection; recombinant virus; regulatory gene; tissue /cell culture; virus genetics; virus infection mechanism

Epstein-Barr virus (EBV) is a human lymphotropic herpesvirus which is the etiologic agent of infectious mononucleosis, and is closely associated with the development of several human cancers. Like Other herpesviruses, EBV can establish either a lytic or latent infection. The proposed research involves characterizing the regulation of the EBV lytic cycle gene BZLF1, which has been shown to be important for induction of the entire lytic cascade. The long-term objectives of these studies are to understand the mechanisms whereby induction of the lytic cycle of EBV is controlled in vivo, and the importance of these mechanisms to viral survival in the host. Proper regulation of lytic induction is likely to be important both for cell-to-cell spread and for immortalization of EBV infected cells. The specific aims of this proposal are 1) Analysis of selected BZLF1 promoter and gene mutations within the context of the viral genome. Selected mutations will be made by homologous recombination, and the effects on induction of the lytic cycle, the formation of immortalized cell lines, and infectivity will be studied. 2) Characterization of the efficiency of induction of the BZLF1 gene in latently infected cells. In situ techniques will be used to compare expression of the BZLF1 gene product with other lytic antigens and with cellular inducible genes to determine whether induction of the lytic cycle is blocked specifically at BZLF1 gene expression. The applicant has developed this proposal with an objective to become an established, independent investigator of the Epstein-Barr virus. The applicant will devote 100% effort to the proposed research for the duration of this award, in order to maximize the potential to realize this objective. The sponsor's laboratory was chosen on the basis of scientific merit, enthusiasm, knowledge of EBV, availability of resources, and dedication to the applicant; in addition there is a strong Community of virologists and immunologists at this institution whose expertise will be invaluable to the applicant's scientific development.

EB 病毒 (EBV) 是一种人类嗜淋巴细胞疱疹病毒， 传染性单核细胞增多症的病原体，与传染性单核细胞增多症密切相关 随着几种人类癌症的发展。与其他疱疹病毒一样， EBV 可以建立溶解性或潜伏性感染。拟议的 研究涉及 EBV 裂解循环调节的特征 基因 BZLF1，已被证明对于诱导 整个裂解级联。这些研究的长期目标是 了解诱导 EBV 裂解循环的机制 体内控制，以及这些机制对病毒的重要性 在宿主体内生存。裂解诱导的适当调节可能 对于细胞间传播和 EBV 永生化都很重要 被感染的细胞。该提案的具体目标是 1) 分析 选择的 BZLF1 启动子和基因突变 病毒基因组。选定的突变将由同源基因产生 重组，以及对裂解周期诱导的影响， 将研究永生化细胞系的形成和感染性。 2) BZLF1基因诱导效率的表征 潜伏感染的细胞。将使用现场技术进行比较 BZLF1 基因产物与其他裂解抗原的表达 细胞诱导基因以确定是否诱导裂解 循环在 BZLF1 基因表达处被特异性阻断。 申请人制定本提案的目的是成为 成立，爱泼斯坦-巴尔病毒的独立调查员。这 申请人将投入100%的努力来进行拟议的研究 该奖项的持续时间，以最大限度地发挥实现潜力 这个目标。选择申办者实验室的依据是 科学价值、热情、EBV 知识、可用性 资源以及对申请人的奉献精神；此外还有一个强大的 该机构的病毒学家和免疫学家社区 专业知识对于申请人的科学发展来说是无价的。

项目成果

Murine gamma-herpesvirus 68 causes severe large-vessel arteritis in mice lacking interferon-gamma responsiveness: a new model for virus-induced vascular disease.

鼠伽马疱疹病毒 68 在缺乏干扰素伽马反应性的小鼠中引起严重的大血管动脉炎：病毒诱发的血管疾病的新模型。

• DOI: 10.1038/nm1297-1346
• 发表时间: 1997
• 期刊: Nature medicine
• 影响因子: 82.9
• 作者: Weck,KE;DalCanto,AJ;Gould,JD;O'Guin,AK;Roth,KA;Saffitz,JE;Speck,SH;Virgin,HW
• 通讯作者: Virgin,HW