TRANSACTIVATION OF CD23 BY EBNA-2 AND LMP

EBNA-2 和 LMP 对 CD23 的反激活

• 批准号: 3085880
• 负责人: SO F TSANG
• 金额: $ 9.21万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-01 至 1993-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3085880
• 关键词: B lymphocyte; CD antigens; DNA binding protein; DNA footprinting; Epstein Barr virus; antisense nucleic acid; cell transformation; gene deletion mutation; gene expression; genetic manipulation; genetic transcription; latent virus infection; leukocyte activation /transformation; membrane proteins; molecular cloning; nuclear runoff assay; nucleoproteins; point mutation; tissue /cell culture; transcription factor; transforming virus; virus antigen; virus protein

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

爱泼斯坦-巴尔病毒（EBV）是一种疱疹病毒，可引起鼻咽炎