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.