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。尽管可以在组织培养中通过刺激B细胞受体（使用抗免疫球蛋白）或TGF-β受体（使用异位TGF-β）来实现EB病毒的再激活，但尚不确定此类事件在体内EB病毒感染的淋巴细胞中的常见程度（来自大卫的工作Thorley-Lawson的实验室）。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。

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.