Intercellular communication in Epstein Barr virus reactivation

描述（由申请人提供）：eb病毒（EBV）在艾滋病相关的非霍奇金淋巴瘤中具有高渗透性，是肿瘤表型的关键驱动因素。虽然EBV潜伏期基因对促进肿瘤表型至关重要，但从潜伏期到裂解周期的转换是EBV感染计划成功的关键方面。因此，推动这种转变的机制多年来一直是积极研究的主题。虽然EBV再激活可以通过刺激b细胞受体（抗ig）或tgf - β受体（异位tgf - β）在组织培养中实现，但尚不确定这种事件在体内EBV感染淋巴细胞中有多常见（David Thorley-Lawson实验室的工作）。这一应用的主要假设是EBV进化出了一种感知机制，潜伏感染的b细胞可以在遇到上皮细胞环境时进行检测。该模型提出，来自口腔/扁桃体上皮的环境信号（例如，在生发中心反应的后期）触发b细胞的再激活，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。

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.