Gregory C D, Dive C, Henderson S, Smith C A, Williams G T, Gordon J, Rickinson A B
Department of Immunology, University of Birmingham Medical School, UK.
Nature. 1991 Feb 14;349(6310):612-4. doi: 10.1038/349612a0.
Epstein-Barr virus (EBV), a human herpesvirus, establishes a persistent asymptomatic infection of the circulating B-lymphocyte pool. The mechanism of virus persistence is not understood but, given the limited lifespan of most B cells in vivo, it seems most likely that EBV-infected cells must gain access to the long-lived memory B-cell pool. Here we show in an in vitro system that EBV, through expression of the full set of eight virus-coded 'latent' proteins, can protect human B cells from programmed cell death (apoptosis), the deletion mechanism which normally restricts entry into memory. We have found that EBV-positive Burkitt's lymphoma (BL) cell clones retaining the original tumour cell phenotype and expressing only one of the virus latent proteins, the nuclear antigen EBNA 1, are extremely sensitive to apoptosis; in this respect they resemble the tumour's normal cell of origin found in the germinal centres of lymphoid tissue. By contrast, isogenic BL cell clones which have activated expression of all eight EBV latent proteins are resistant to the induction of apoptosis. The EBV latent proteins should therefore be seen not just as activators of B-cell proliferation but, perhaps more importantly, as mediators of enhanced B-cell survival.
爱泼斯坦-巴尔病毒（EBV）是一种人类疱疹病毒，可在循环B淋巴细胞池中建立持续的无症状感染。病毒持续存在的机制尚不清楚，但鉴于体内大多数B细胞寿命有限，EBV感染的细胞似乎极有可能进入长寿记忆B细胞池。在此，我们在体外系统中表明，EBV通过表达全套八种病毒编码的“潜伏”蛋白，可保护人类B细胞免于程序性细胞死亡（凋亡），而凋亡是通常限制进入记忆细胞的清除机制。我们发现，保留原始肿瘤细胞表型且仅表达一种病毒潜伏蛋白——核抗原EBNA 1的EBV阳性伯基特淋巴瘤（BL）细胞克隆对凋亡极为敏感；在这方面，它们类似于在淋巴组织生发中心发现的肿瘤正常起源细胞。相比之下，激活表达所有八种EBV潜伏蛋白的同基因BL细胞克隆对凋亡诱导具有抗性。因此，EBV潜伏蛋白不应仅仅被视为B细胞增殖的激活剂，或许更重要的是，应被视为增强B细胞存活的介质。
