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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

基本信息

批准号：
6691756
负责人：
S DIANE HAYWARD
金额：
$ 28.72万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
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/6691756
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&apos s lymphoma transcription factor viral carcinogenesis virus genetics virus virus interaction

项目摘要

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 型 (HHV-8)，也称为卡波西肉瘤相关病毒 (KSHV)，于 1994 年首次在艾滋病卡波西肉瘤活检中发现。卡波西肉瘤（KS）是一种相对罕见的血管生成肿瘤，随着艾滋病流行的爆发，其发病率急剧增加。大约 20% 患有艾滋病的男同性恋和双性恋男性会患上 KS。 HHV-8 还始终与 AIDS 患者的其他两种恶性肿瘤相关：多中心卡斯尔曼病和非霍奇金淋巴瘤的一个子集，称为原发性渗出性淋巴瘤 (PEL) 或体腔淋巴瘤 (BCBL)。 PEL 具有一个不寻常的特征，即大多数 PEL 同时感染 HHV-8 和另一种人类 γ 疱疹病毒 Epstein-Barr 病毒 (EBV)。 HHV-8 和 EBV 各自编码多个生长刺激基因，病毒间相互作用可能会调节 HHV-8 或 EBV 基因表达程序，从而导致这种特定恶性肿瘤的发展。该研究项目的目标是更好地了解 PEL 中双重感染的后果。 LANA 是在潜伏感染和所有 HHV-8 相关肿瘤细胞中表达的少数 HHV-8 基因之一。将探讨 LANA 在维持 HHV-8 潜伏期和 PEL 细胞发育中的作用。该提案的具体目标是：目标 1. 将在 PEL 细胞系中检查 EBV 潜伏基因表达、启动子使用、基因组拷贝数和状态（附加型或整合型）。将检查 HHV-8 LANA 调节 EBV 潜伏启动子活性的可能性。目标 2. 将建立 HHV-8 潜伏基因对 PEL 发育的贡献的遗传测定。目标 3. 对 HHV-8 潜伏蛋白 LANA 进行表征，以确定其对 HHV-8 潜伏 DNA 复制的贡献以及通过调节细胞基因表达对肿瘤发生的潜在贡献。