EPSTEIN BARR VIRUS LATENCY

EB病毒(Epstein-Barr Virus，EBV)是一种嗜B淋巴疱疹病毒，通常在感染宿主的一生中持续存在，但也可能导致某些淋巴瘤和癌症的发生。健康携带者外周血中的持续感染是静止的，仅限于潜伏感染的静止记忆B细胞，在这些细胞中，最多表达一到两个潜在基因。相比之下，黏膜淋巴组织中的持续性感染似乎更为复杂。有受感染的幼稚和记忆B细胞，病毒复制产生感染性病毒，以及至少一个全新的亚群，潜伏感染B细胞的频率非常高。病毒并不是通过所有的B细胞亚群随机分布的。我们的假设是，病毒感染细胞的分布可以通过类比次级淋巴组织中正常B细胞的激活和分化来解释。为了验证这一观点，我们将集中在三个主要问题上：1.我们在扁桃体中发现的新的B细胞亚群(CD38 CD10-IGD-)对于潜伏感染的细胞(大约500人中有1人感染)是高度浓缩的，其本质是什么？它与经典定义的记忆B细胞(CD38-CD10-IGD-)有什么关系？2.EBV是一种粘膜特异性病毒，即病毒在淋巴组织中是活跃的，还是在除粘膜淋巴组织之外的所有地方都处于静止状态？病毒是在所有淋巴组织中复制还是仅在粘膜淋巴组织中复制？3.淋巴组织中的病毒感染细胞是否能够经历生发中心反应进入记忆室。

Epstein-Barr virus (EBV) is a B lymphotropic herpesvirus that usually persists benignly for the life time of the infected host, but can be predisposing for the development of certain lymphomas and carcinomas. Persistent infection in the peripheral blood of healthy carriers is quiescent, being restricted to latently infected, resting, memory B cells in which, at most, one or two latent genes are expressed. By comparison persistent infection in the mucosal lymphoid tissue appears to be more complex. There are infected naive and memory B cells, viral replication to produce infectious virus and at least one completely novel subset with a very high frequency of latently infected B cells. The virus is not randomly distributed through all of the B cells subsets. It is our hypothesis that the distribution of virus infected cells can be explained through analogy to normal B cell activation and differentiation within secondary lymphoid tissue. To test this idea we will focus on three main issues: 1. What is the nature of the novel B cell subset (CD38+CD10-IgD-) that we have found in the tonsils to be highly enriched for latently infected cells (approximately 1 in 500 are infected) and what is its relationship to classically defined memory B cells (CD38- CD10-IgD-) 2. Is EBV a mucosal specific virus i.e. is viral persistence actively maintained throughout the lymphoid tissue or quiescent everywhere except mucosal lymphoid tissue? Does the virus replicate in all lymphoid tissue or only mucosal lymphoid tissue? 3. Are virus infected cells in the lymphoid tissue able to undergo a germinal center reaction to enter the memory compartment.