EBV AND HHV-8 INTERACTIONS IN PRIMARY EFFUSION LYMPHOMAS

原发性渗出性淋巴瘤中 EBV 和 HHV-8 的相互作用

• 批准号: 6078539
• 负责人: S DIANE HAYWARD
• 金额: $ 26.3万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-19 至 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6078539
• 关键词: AIDS related neoplasm /cancer; Epstein Barr virus; antiserum; cell line; gene expression; human herpesvirus 8; laboratory rabbit; latent virus infection; neoplasm /cancer genetics; nonHodgkin's lymphoma; transcription factor; viral carcinogenesis; virus genetics; virus virus interaction

Human herpesvirus 8 (HHV-8), also called Kaposi's sarcoma- associated virus (KSHV), was first identified in 1994 in AIDS Kaposi's sarcoma biopsies. Kaposi's sarcoma (KS) was a relatively rare angiogenic neoplasm that dramatically increased in incidence with the onset of the AIDS epidemic. Approximately 20 percent of gay and bisexual men with AIDS develop KS. HHV-8 is also consistently assoicated with two other malignancies in AIDS patients: Multicentric Castleman's disease and a subset of non-Hodgkin's lymphomas called primary effusion lymphomas (PELs) or body cavity based lymphomas (BCBLs). PELs have the unusual feature that the majority are co-infected with both HHV-8 and another human gamma herpesvirus Epstein-Barr virus (EBV). HHV-8 and EBV each encode multiple growth stimulatory genes and the potential exists for inter-virus interactions that modulate the program of HHV-8 or EBV gene expression to allow the development of this particular malignancy. A goal of this research project is to better understand the consequences of dual infection in PELs. LANA is one of the few HHV-8 genes that is expressed in latent infection and in all HHV-8 associated tumor cells. LANA's role in the maintenance of HHV-8 latency and in PEL cell development will be explored. The Specific Aims of this proposal are: Aim 1. EBV latency gene expression, promoter usage, genome copy number and status (episomal or integrated) will be examined in PEL cell lines. The possibility that HHV-8 LANA can modulate EBV latency promoter activity will be examined. Aim 2. A genetic assay for the contribution of HHV-8 latency genes to PEL development will be established. Aim 3. The HHV-8 latency protein LANA will be characterized to determine its contribution to HHV-8 latency DNA replication and its potential contribution to tumorigenesis through modulation of cellular gene expression.

人类疱疹病毒8（HHV-8），也称为Kaposi的肉瘤相关病毒（KSHV），于1994年在AIDS KAPOSI的肉瘤活检中首次鉴定出来。 卡波西（Kaposi）的肉瘤（KS）是一种相对罕见的血管生成肿瘤，随着艾滋病流行病的发作，其发生率大大增加。 大约有20％的同性恋者和双性恋男性患有艾滋病。 HHV-8在艾滋病患者中也始终与另外两个恶性肿瘤相结合：多中心castleman病和一部分为非霍奇金淋巴瘤，称为原发性积液淋巴瘤（PELS）或基于体腔的淋巴瘤（BCBLS）。 Pels具有不寻常的特征，即大多数人都与HHV-8和另一个人类Gamma疱疹病毒Epstein-Barr病毒（EBV）共感染。 HHV-8和EBV每个编码多个生长刺激基因，并且存在用于调节HHV-8或EBV基因表达程序的病毒间相互作用的潜力，以允许这种特定的恶性肿瘤的发展。 该研究项目的一个目标是更好地了解PELS双重感染的后果。 LANA是在潜在感染和所有HHV-8相关肿瘤细胞中表达的少数HHV-8基因之一。 Lana将在维持HHV-8潜伏期和PEL细胞开发中的作用。该提案的具体目的是：目标1。EBV潜伏基因表达，启动子使用，基因组拷贝数和状态（偶发或集成）将在PEL细胞系中检查。 HHV-8 LANA可以调节EBV潜伏期启动子活动的可能性。 目标2。将建立HHV-8潜伏基因对PEL发育的贡献的遗传测定。 AIM 3。将对HHV-8潜伏期LANA进行表征，以确定其对HHV-8潜伏期DNA复制的贡献，并通过调节细胞基因表达来确定其对肿瘤发生的潜在贡献。