TRANSACTIVATION OF CD23 BY EBNA-2 AND LMP

EB病毒是一种能引起鼻咽部疾病的疱疹病毒。 癌，非洲Burkitt淋巴瘤，单克隆性和多克隆性 免疫受损宿主的淋巴增生性疾病。EB病毒 优先感染正常的B淋巴细胞并导致快速和 B淋巴细胞向永生化细胞系的高效转化。 6种核蛋白：EBNA-1、EBNA-2、EBNA-3A、EBNA-3B、EBNA-3C、EBNA-LP、 和一种膜蛋白LMP；在潜伏感染的生长中表达- 转化的淋巴细胞。 通过基因分析，EBNA-2已被证明是诱导EBV所必需的 转型。EBNA-2促进生长的确切机制 转型仍是未知数。EBNA-2的表型变化 生长并可能通过特异性诱导细胞CD23基因发挥作用 表情。EB病毒感染后24小时内B细胞表面检测到CD23 感染。永生化B细胞几乎完全来源于CD23 阳性细胞群。LMP是潜伏性的膜蛋白，具有直接的 协同诱导CD23在鼠成纤维细胞中的转化能力 BJAB细胞(EBV阴性的Burkitt淋巴瘤细胞)。对……的详细研究 EBNA-2和LMP对细胞CD23的反式激活机制 使我们了解这些潜伏的基因是如何对B淋巴细胞起作用的 转化以及正常的B细胞生长调节。 具体地说，该提案的目标是确定： (1)EBNA-2和LMP诱导CD23的机制； (2)转化所必需的EBNA-2结构域和CD23 激活 (3)CD23表达在EBV诱导的生长转化中的作用 CD23的过度表达和抑制

Epstein-Barr virus (EBV) is a herpes virus which can cause nasopharyngeal carcinoma, African Burkitt's lymphoma, monoclonal and polyclonal lymphoproliferative disorders in immunocompromised host. EBV preferentially infects normal B lymphocytes and results in rapid and efficient transformation of B lymphocytes into immortalized cell lines. Six nuclear proteins: EBNA-1, EBNA-2, EBNA-3A, EBNA-3B, EBNA-3C, EBNA-LP, and one membrane protein LMP; are expressed in latently infected growth- transformed lymphocytes. By genetic analysis, EBNA-2 has been shown to be essential for EBV induced transformation. The exact mechanism by which EBNA-2 contributes to growth transformation is still unknown. EBNA-2 confers a phenotypic change in growth and may function by specifically inducing cellular CD23 gene expression. CD23 was detected on B cell surface within 24 hours after EBV infection. Immortalized B cells arise almost exclusively from CD23 positive cell population. LMP, the latent membrane protein, has direct transforming ability in rodent fibroblast, cooperatively induces CD23 in BJAB cells (EBV negative Burkitt's lymphoma cells). Detailed studies of the transactivation mechanism of cellular CD23 by EBNA-2 and LMP will enable us to understand how these latent genes contribute to B lymphocyte transformation as well as normal B cell growth regulation. Specifically, the goals of this proposal are to determine: (1) the mechanism by which EBNA-2 and LMP induce CD23, (2) the EBNA-2 domains essential for transformation and CD23 transactivation (3) the role of CD23 expression in EBV induced growth transformation, both by overexpression and inhibition of CD23