ROLE OF EBNA-LP IN EBV-INDUCED TRANSFORMATION

EBNA-LP 在 EBV 诱导的转化中的作用

• 批准号: 3085393
• 负责人: JOAN B MANNICK
• 金额: $ 9.15万
• 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: 1990-09-30 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3085393
• 关键词: B lymphocyte; Burkitt's lymphoma; Epstein Barr virus; RNA biosynthesis; RNA splicing; biological models; carcinoma; gene expression; genetic manipulation; immunosuppression; latent virus infection; mutant; nasopharyngeal neoplasms; neoplastic growth; nucleoproteins; protein structure function; sarcoma; viral carcinogenesis; virus genetics; virus replication

Epstein-Barr virus (EBV) is a human herpes virus associated with a variety of tumors including African Burkitt lymphoma, nasopharyngeal carcinoma and immunoblastic sarcoma in immunosuppressed patients. EBV usually establishes a latent infection in B lymphocytes and stimulates them to proliferate. Sustained polyclonal proliferation of EBV infected cells in vivo may occasionally result in monoclonal malignancies. In vitro, B cells are immortalized and provide a model with which to study EBV-induced tumorigenicity. Although the EBV genome contains about 100 genes, only 10 of these are known to be expressed in latently infected, growth transformed lymphocytes. These genes are of interest because they are likely to be involved in the immortalization of lymphocytes as well as in the maintenance of viral latency. One of the genes is the EBV nuclear antigen leader protein (EBNA-LP). The function of EBNA-LP is unknown although preliminary experiments have shown that deletion of the last two exons of EBNA-LP results in a marked reduction in the growth rate of transformed cells. The aim of the proposed studies is to determine the function of EBNA-LP. Recombinant viruses will be constructed with mutations in EBNA-LP using techniques which our laboratory has used successfully to construct recombinant EBV with mutations in the EBNA2 gene. We then will determine if the mutations in EBNA-LP alter growth rate, RNA metabolism or protein expression of cells transformed by EBV. Finally we will analyze whether transfection of wild-type EBNA-LP into cells expressing mutant EBNA-LP can recreate a wild type phenotype, thus confirming that alterations in phenotype are due to the EBNA-LP mutations. Elucidation of the function of EBNA-LP will lead to a better understanding of EBV-induced transformation which in turn may increase our understanding of oncogenesis.

EB病毒(Epstein-Barr Virus，EBV)是一种与多种人类疱疹病毒相关的病毒 肿瘤包括非洲Burkitt淋巴瘤，鼻咽癌和 免疫抑制患者的免疫母细胞性肉瘤。EBV通常会建立 B淋巴细胞中的一种潜伏感染并刺激它们增殖。 EBV感染细胞体内持续多克隆增殖可能 偶尔会导致单克隆性恶性肿瘤。在体外，B细胞是 永垂不朽，并提供了研究EBV诱导的模型 致瘤性。 尽管EBV基因组包含大约100个基因，但其中只有10个是 已知在潜伏感染、生长转化的淋巴细胞中表达。 这些基因之所以令人感兴趣，是因为它们可能参与了 淋巴细胞永生化以及病毒的维持 延迟。其中一个基因是EB病毒核抗原前导蛋白。 (EBNA-LP)。EBNA-LP的功能尚不清楚，虽然初步 实验表明，EBNA-LP最后两个外显子的缺失 导致转化细胞的生长速度显著降低。这个 本研究的目的是确定EBNA-LP的功能。 利用EBNA-LP中的突变构建重组病毒 我们实验室已经成功使用的技术 EBNA2基因突变的重组EBV。然后我们将确定是否 EBNA-LP的突变改变了生长速度、RNA代谢或蛋白质 EB病毒转化细胞的表达。最后，我们将分析是否 野生型EBNA-LP导入表达突变型EBNA-LP的细胞 重新创造了野生型表型，从而证实了 表型是由于EBNA-LP突变所致。对其功能的阐释 EBNA-LP将有助于更好地理解EBV诱导的转化 这反过来可能会增加我们对肿瘤发生的理解。