Intercellular communication in Epstein Barr virus reactivation

Epstein Barr 病毒重新激活中的细胞间通讯

• 批准号: 8341401
• 负责人: ERIK K FLEMINGTON
• 金额: $ 37.63万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-10 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8341401
• 关键词: AIDS-Related Non-Hodgkin' s Lymphoma; Automobile Driving; B-Lymphocytes; Cell Communication; Cells; Complex; Cues; Environment; Epithelial; Epithelial Cells; Epithelium; Epstein-Barr Virus Infections; Epstein-Barr Virus latency; Event; Family; Fractionation; Genes; Human Herpesvirus 4; Investigation; Life; Lymphocyte; Lytic Phase; Mediating; Membrane; Microscopy; Modeling; Oral; Pathway interactions; Phenotype; Porifera; Proteomics; RNA; Reaction; Receptors, Antigen, B-Cell; Regulatory Pathway; Role; Saliva; Series; Staging; Structure of germinal center of lymph node; Tonsil; Transforming Growth Factor beta; Transforming Growth Factor beta Receptors; Vesicle; Viral; Virus; Virus Latency; Work; cellular imaging; comparative efficacy; in vivo; infected B cell; intercellular communication; oral cavity epithelium; programs; response; retroviral transduction; tissue culture; trafficking; transmission process; tumor

DESCRIPTION (provided by applicant): The Epstein-Barr virus (EBV) is highly penetrant in AIDS-associated non-Hodgkin's lymphomas where it is a key driver of the tumor phenotype. While EBV latency genes are critical for facilitating the tumor phenotype, the switch from latency to the lytic cycle is a critical aspect of a successful EBV infection program. As a result, the mechanisms driving this switch have been topics of active investigation over the years. Although EBV reactivation can be achieved in tissue culture through stimulation of the B-cell receptor (with anti-Ig) or the TGF-beta receptor (with ectopic TGF-beta), it is uncertain how common such events are in EBV-infected lymphocytes in vivo (work from David Thorley-Lawson's lab). The overarching hypothesis of this application is that EBV has evolved with a sensing mechanism for latently infected B-cells to detect when they encounter an epithelial cell environment. This model proposes that environmental cues from the oral/tonsil epithelium (in the late stages of the germinal center reaction, for example) trigger reactivation in B-cells, thereby facilitating the B-cell to epithelial cell viral transfer that is a fundamental first step n oral epithelial plaque formation and host- to-host transmission. PUBLIC HEALTH RELEVANCE: The EBV infection cascade involves a complex series of events. A critical component of host-to-host transmission is the transfer of virus from B-cells harboring the latency viral reservoir to the oral epithelium where infectious virus is amplified an secreted into the saliva. We hypothesize that this transfer is orchestrated, in part, through cell o cell communication between epithelial cells and latently infected B-cells to increase the efficiency of this exchange pathway.

描述（由申请人提供）：EB病毒（EBV）在艾滋病相关非霍奇金淋巴瘤中具有高度渗透性，是肿瘤表型的关键驱动因素。虽然EBV潜伏基因对于促进肿瘤表型至关重要，但从潜伏期到裂解周期的转换是成功的EBV感染程序的关键方面。因此，驱动这种转换的机制多年来一直是积极研究的主题。虽然EB病毒再活化可以通过刺激B细胞受体（抗Ig）或TGF-β受体（异位TGF-β）在组织培养中实现，但目前还不确定这种事件在体内EB病毒感染的淋巴细胞中有多常见（大卫Thorley-Lawson实验室的工作）。本申请的首要假设是EBV已经进化出潜伏感染的B细胞的传感机制，以检测它们何时遇到上皮细胞环境。该模型提出，来自口腔/扁桃体上皮的环境线索（例如，在生发中心反应的晚期）触发B细胞的再活化，从而促进B细胞到上皮细胞的病毒转移，这是口腔上皮斑块形成和宿主到宿主传播的基本第一步。 公共卫生相关性：EBV感染级联涉及一系列复杂的事件。宿主间传播的一个关键组成部分是病毒从携带潜伏病毒库的B细胞转移到口腔上皮，在口腔上皮中感染性病毒被扩增并分泌到唾液中。我们假设这种转移是精心策划的，部分是通过上皮细胞和潜伏感染的B细胞之间的细胞对细胞的通信，以增加这种交换途径的效率。