Viral Transcription in EBV Transformed B Cells

EBV 转化的 B 细胞中的病毒转录

基本信息

批准号：
7046107
负责人：
SAMUEL H SPECK
金额：
$ 27.81万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-07-01 至 2007-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7046107
关键词：
B lymphocyte Callithricidae DNA methylation Epstein Barr virus cell transformation clinical research gene expression gene mutation genetic regulatory element genetic transcription host organism interaction human subject latent virus infection recombinant virus tissue /cell culture transfection transforming virus virus genetics

项目摘要

DESCRIPTION (provided by applicant): This is a competing renewal of an ROl grant with the long term goal of understanding how Epstein-Barr virus (EBV) gene expression is regulated during immortalizing latency. EBV establishes a life-long infection within the infected host, and is closely associated with the development of endemic Burkitt's lymphoma, nasopharyngeal carcinoma, 30-50 percent of Hodgkin's disease, and nearly half of the lymphomas that arise in immunosuppressed patients. Notably, EBV infection of peripheral resting B cells results in growth transformation resulting, ex vivo, in the generation of immortalized lymphoblastoid cell lines. Based on recent analyses of EBV infection in seropositive individuals, it seems likely that the ability of EBV to drive B cell proliferation, and subsequent differentiation, plays an important role in the dissemination of virus infected B cells and the establishment of a long-lived latency reservoir in memory B cells (in which there is very limited viral gene expression). Understanding how EBV regulates viral gene expression during immortalizing latency may ultimate provide strategies for interfering with this phase of the virus life cycle, which could interfere with the establishment of latency in the memory B cell compartment. Within the scope of this proposal, we will continue to focus our analyses on identifying and characterizing cis-elements involved in regulated EBNA gene expression during the immortalizing latency program of EBV. Aim 1. Generation of a cottontop marmoset LCL immortalized with a packaging defective and replication null EBV to serve as an inducible reservoir for non-immortalizing EBV mutants. Aim 2. Generation and characterization of EBV harboring mutations in cis-elements thought to be involved in regulating EBNA gene transcription in EBV immortalized lymphoblastoid cell lines. Aim 3. Analysis of the requirements for Wp activity during initial stages of infection of primary B cells. Aim 4. Analysis of Wp methylation during the establishment and maintenance of immortalizing latency in B cells - role of methylation in regulating Wp activity in lymphoblastoid cell lines.

描述（由申请人提供）：这是 ROl 的竞争性更新资助的长期目标是了解 Epstein-Barr 病毒 (EBV) 基因表达在永生潜伏期受到调节。 EBV 建立了受感染宿主体内终生感染，并且与地方性伯基特淋巴瘤、鼻咽癌的发展，30-50 霍奇金病的百分比，以及近一半的淋巴瘤免疫抑制患者。值得注意的是，外周静息 B 细胞的 EBV 感染导致生长转化，离体产生永生化淋巴母细胞系。基于最近的 EBV 分析血清阳性个体感染后，EBV 的能力似乎很可能驱动 B 细胞增殖和随后的分化，起着在病毒感染的 B 细胞的传播中发挥着重要作用在记忆 B 细胞中建立长寿命潜伏期储存库（其中病毒基因表达非常有限）。了解 EBV 如何调节永生潜伏期的病毒基因表达可能最终提供干扰病毒生命周期这一阶段的策略，这可能干扰记忆 B 细胞区室中潜伏期的建立。在本提案的范围内，我们将继续重点分析鉴定和表征参与调节的 EBNA 基因的顺式元件 EBV永生化潜伏期期间的表达。目标 1. 生成通过包装永生的棉顶狨猴拼箱有缺陷和复制无效的 EBV 可作为诱导型储存库非永生化 EBV 突变体。目标 2. 携带突变的 EBV 的产生和表征顺式元件被认为参与调节 EBNA 基因转录 EBV 永生化淋巴母细胞系。目标 3. 分析初始阶段对 Wp 活性的需求原代B细胞的感染。目标 4. 在建立和维持过程中分析 Wp 甲基化 B 细胞的永生潜伏期 - 甲基化在调节 Wp 中的作用类淋巴母细胞系中的活性。

项目成果

期刊论文数量（52）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Determining the role of the Epstein-Barr virus Cp EBNA2-dependent enhancer during the establishment of latency by using mutant and wild-type viruses recovered from cottontop marmoset lymphoblastoid cell lines.

使用从棉顶狨猴淋巴母细胞系中回收的突变型和野生型病毒确定 Epstein-Barr 病毒 Cp EBNA2 依赖性增强子在潜伏期建立过程中的作用。

DOI：
10.1128/jvi.74.23.11115-11120.2000
发表时间：
2000
期刊：
Journal of virology
影响因子：
5.4
作者：
Yoo,L;Speck,SH
通讯作者：
Speck,SH

Exclusive expression of Epstein-Barr virus nuclear antigen 1 in Burkitt lymphoma arises from a third promoter, distinct from the promoters used in latently infected lymphocytes.

伯基特淋巴瘤中 Epstein-Barr 病毒核抗原 1 的独家表达源自第三个启动子，该启动子与潜伏感染淋巴细胞中使用的启动子不同。

DOI：
10.1073/pnas.88.15.6550
发表时间：
1991
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Schaefer,BC;Woisetschlaeger,M;Strominger,JL;Speck,SH
通讯作者：
Speck,SH

Inhibition of NF-kappaB activation in vivo impairs establishment of gammaherpesvirus latency.