Interactions of KSHV and endothelial cells

KSHV 与内皮细胞的相互作用

基本信息

批准号：
7197321
负责人：
Michael Lagunoff
金额：
$ 24.97万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-04-01 至 2008-09-21
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7197321
关键词：
Africa B-Lymphocytes Biology Cell Line Cells Common Neoplasm Conditioned Culture Media Country Cytolysis Defect Dominant-Negative Mutation Endothelial Cells Ensure Ganciclovir Gene Expression Gene Expression Regulation Genes Genetic Transcription Genome Growth Herpesviridae Herpesviridae Infections Highly Active Antiretroviral Therapy Human Herpesvirus 8 Infection Kaposi Sarcoma Latent virus infection phase Lead Life Lymphoma Lymphoproliferative Disorders Lytic Lytic Phase Maintenance Masks Neoplasms Numbers Open Reading Frames Pathogenesis Patients Phase Play Property Protein Overexpression RNA Recombinants Reporting Role Signal Pathway Signal Transduction Simplexvirus System Testing Time Viral Virus Virus Diseases base cell growth effusion in vivo latent infection lytic gene expression lytic replication mutant neoplastic cell paracrine particle research study sarcoma tumor

项目摘要

DESCRIPTION (provided by applicant): Kaposi's Sarcoma (KS) was the most common tumor in Aids patients in this country before the wide spread use of highly active antiretroviral therapy. KS is currently the most commonly reported tumor in regions of Africa. Kaposi's Sarcoma-associated herpesvirus (KSHV, formally known as human herpesvirus 8, HHV-8) is an essential etiologic agent for KS. In KS, KSHV is found in the spindle cell, a cell of endothelial origin that is the tumor cell of KS. KSHV is also associated with primary effusion lymphoma (PEL), a B-cell lymphoproliferative disorder. PEL cell lines have been created and are used for many studies of KSHV. However, KS is an endothelial cell based neoplasm and thus it is important to study KSHV in endothelial cells as well. Herpesviruses are all characterized by having latent infection, where the virus is maintained for the life of the host but does not produce infectious particles, and lytic infection, where the virus replicates and lyses the host cell. Interestingly, KS apparently requires both lytic and latent phase infection for formation and maintenance. Since the lytically infected cell is dying, there must be paracrine factors produced that act on latently infected cells. We propose to characterize the function of lytic gene expression in maintenance of KS by studying the role of lytic genes in latently infected endothelial cells. We have created a tractable system for studying KSHV in endothelial cells and we will study KSHV gene expression and function in our endothelial cell system. We will create and purify recombinant KSHV isolates deleted in prominent lytic genes involved in signal transduction. Subsequent analysis will characterize the role of these genes in both lytic and latent infection. We will analyze growth and signaling capabilities during lytic infection and we will analyze how these lytic genes alter host transcription in latently infected cells.

描述（由申请人提供）：在广泛使用高效抗逆转录病毒疗法之前，卡波西肉瘤（KS）是该国艾滋病患者中最常见的肿瘤。 KS 是目前非洲地区最常见的肿瘤。卡波西肉瘤相关疱疹病毒（KSHV，正式名称为人类疱疹病毒 8 型，HHV-8）是 KS 的重要病原体。在 KS 中，KSHV 存在于梭形细胞中，梭形细胞是一种内皮来源的细胞，也是 KS 的肿瘤细胞。 KSHV 还与原发性渗出性淋巴瘤 (PEL)（一种 B 细胞淋巴增殖性疾病）相关。 PEL 细胞系已被创建并用于 KSHV 的许多研究。然而，KS 是一种基于内皮细胞的肿瘤，因此研究内皮细胞中的 KSHV 也很重要。疱疹病毒的特征都是具有潜伏感染（病毒在宿主的一生中保留但不产生感染性颗粒）和裂解性感染（病毒复制并裂解宿主细胞）。有趣的是，KS 显然需要裂解期感染和潜伏期感染才能形成和维持。由于被裂解感染的细胞正在死亡，因此必须产生作用于潜伏感染细胞的旁分泌因子。我们建议通过研究裂解基因在潜伏感染的内皮细胞中的作用来表征裂解基因表达在 KS 维持中的功能。我们已经创建了一个用于研究内皮细胞中 KSHV 的易于处理的系统，我们将研究内皮细胞系统中 KSHV 基因的表达和功能。我们将创建并纯化重组 KSHV 分离株，其中删除了参与信号转导的重要裂解基因。随后的分析将表征这些基因在裂解感染和潜伏感染中的作用。我们将分析裂解感染期间的生长和信号传导能力，并将分析这些裂解基因如何改变潜伏感染细胞中的宿主转录。